Performance of SARS COV-2 IgG Anti-N as an Independent Marker of Exposure to SARS COV-2 in an Unvaccinated West African Population.

Determination of previous SARS-COV-2 infection is hampered by the absence of a standardized test. The marker used to assess previous exposure is IgG antibody to the nucleocapsid (IgG anti-N), although it is known to wane quickly from peripheral blood. The accuracies of seven antibody tests (virus neutralization test, IgG anti-N, IgG anti-spike [anti-S], IgG anti-receptor binding domain [anti-RBD], IgG anti-N + anti-RBD, IgG anti-N + anti-S, and IgG anti-S + anti-RBD), either singly or in combination, were evaluated on 502 cryopreserved serum samples collected before the COVID-19 vaccination rollout in Kumasi, Ghana. The accuracy of each index test was measured using a composite reference standard based on a combination of neutralization test and IgG anti-N antibody tests. According to the composite reference, 262 participants were previously exposed; the most sensitive test was the virus neutralization test, with 95.4% sensitivity (95% CI: 93.6-97.3), followed by 79.0% for IgG anti-N + anti-S (95% CI: 76.3-83.3). The most specific tests were virus neutralization and IgG anti-N, both with 100% specificity. Viral neutralization and IgG anti-N + anti-S were the overall most accurate tests, with specificity/sensitivity of 100/95.2% and 79.0/92.1%, respectively. Our findings indicate that IgG anti-N alone is an inadequate marker of prior exposure to SARS COV-2 in this population. Virus neutralization assay appears to be the most accurate assay in discerning prior infection. A combination of IgG anti-N and IgG anti-S is also accurate and suited for assessment of SARS COV-2 exposure in low-resource settings.

Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.

BACKGROUND: Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa. AIMS: We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen. METHODS: WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy. RESULTS: Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility-this was characterized by the T66A, G118R, E138K and R263K mutations. CONCLUSIONS: This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.

Costs of HIV prevention services provided by community-based organizations to female sex workers in Nigeria.

BACKGROUND: Nigeria has been consistently targeted in sub-Saharan Africa as an HIV-priority country. Its main mode of transmission is heterosexual, and consequently, a key population of interest is female sex workers (FSWs). While HIV prevention services are increasingly implemented by community-based organizations (CBOs) in Nigeria, there is a paucity of evidence on the implementation costs of these organizations. This study seeks to fill this gap by providing new evidence about service delivery unit cost for HIV education (HIVE), HIV counseling and testing (HCT), and sexually transmitted infection (STI) referral services. METHODS: In a sample of 31 CBOs across Nigeria, we calculated the costs of HIV prevention services for FSWs taking a provider-based perspective. We collected 2016 fiscal year data on tablet computers during a central data training in Abuja, Nigeria, in August 2017. Data collection was part of a cluster-randomized trial examining the effects of management practices in CBOs on HIV prevention service delivery. Staff costs, recurrent inputs, utilities, and training costs were aggregated and allocated to each intervention to produce total cost calculations, and then divided by the number of FSWs served to produce unit costs. Where costs were shared across interventions, a weight proportional to intervention outputs was applied. All cost data were converted to US dollars using the mid-year 2016 exchange rate. We also explored the cost variation across the CBOs, particularly the roles of service scale, geographic location, and time. RESULTS: The average annual number of services provided per CBO was 11,294 for HIVE, 3,326 for HCT, and 473 for STI referrals. The unit cost per FSW tested for HIV was 22 USD, the unit cost per FSW reached with HIV education services was 19 USD, and the unit cost per FSW reached by STI referrals was 3 USD. We found heterogeneity in total and unit costs across CBOs and geographic location. Results from the regression models show that total cost and service scale were positively correlated, while unit costs and scale were consistently negatively correlated; this indicates the presence of economies of scale. By increasing the annual number of services by 100 percent, the unit cost decreases by 50 percent for HIVE, 40 percent for HCT, and 10 percent for STI. There was also evidence that indicates that the level of service provision was not constant over time across the fiscal year. We also found unit costs and management to be negatively correlated, though results were not statistically significant. CONCLUSIONS: Estimates for HCT services are relatively similar to previous studies. There is substantial variation in unit costs across facilities, and evidence of a negative relationship between unit costs and scale for all services. This is one of the few studies to measure HIV prevention service delivery costs to female sex workers through CBOs. Furthermore, this study also looked at the relationship between costs and management practices-the first of its kind to do so in Nigeria. Results can be leveraged to strategically plan for future service delivery across similar settings.

Effect of Nigeria Presidential Task Force on COVID-19 Pandemic, Nigeria.

Nigeria had a confirmed case of COVID-19 on February 28, 2020. On March 17, 2020, the Nigerian Government inaugurated the Presidential Task Force (PTF) on COVID-19 to coordinate the country's multisectoral intergovernmental response. The PTF developed the National COVID-19 Multisectoral Pandemic Response Plan as the blueprint for implementing the response plans. The PTF provided funding, coordination, and governance for the public health response and executed resource mobilization and social welfare support, establishing the framework for containment measures and economic reopening. Despite the challenges of a weak healthcare infrastructure, staff shortages, logistic issues, commodity shortages, currency devaluation, and varying state government cooperation, high-level multisectoral PTF coordination contributed to minimizing the effects of the pandemic through early implementation of mitigation efforts, supported by a strong collaborative partnership with bilateral, multilateral, and private-sector organizations. We describe the lessons learned from the PTF COVID-19 for future multisectoral public health response.

SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa.

Real-world data on vaccine-elicited neutralising antibody responses for two-dose AZD1222 in African populations are limited. We assessed baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using binding antibodies analysis coupled with pseudotyped virus neutralisation assays in two cohorts from West Africa: Nigerian healthcare workers (n = 140) and a Ghanaian community cohort (n = 527) pre and post vaccination. We found 44 and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59 and 39% respectively with anti-receptor binding domain (RBD) IgG-specific antibodies. Previous IgG anti-N positivity significantly increased post two-dose neutralizing antibody titres in both populations. Serological evidence of breakthrough infection was observed in 8/49 (16%). Neutralising antibodies were observed to wane in both populations, especially in anti-N negative participants with an observed waning rate of 20% highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.

Introducing biomarkers for invasive fungal disease in haemato-oncology patients: a single-centre experience.

Hypothesis/Gap Statement. The impacts of increased biomarker testing on antifungal prescribing have not yet been fully examined in a real-life setting.Objectives. Biomarkers for invasive fungal disease (IFD) have been shown to reduce antifungal prescriptions in neutropaenic haemato-oncology patients. Our study aimed to assess the real-life impacts of introducing a novel biomarker-based pathway, incorporating serum galactomannan and Aspergillus PCR, for pyrexial haemato-oncology admissions.Methods. Patients with neutropaenic fever were identified prospectively after introduction of the new pathway from 2013-2015. A historical group of neutropaenic patients who had blood cultures taken from 2009-2012 was generated for comparison. Clinical details, including demographics, underlying diagnosis, investigations, radiology and antimicrobial treatment were obtained.Results. Prospective data from 308 patients were compared to retrospective data from 302 patients. The proportion of patients prescribed an antifungal medication was unchanged by the pathway (P=0.79), but the pattern was different, with more patients receiving targeted antifungals (P=0.04). A negative serum galactomannan test was not sufficient evidence to withhold therapy, with 17.2% of these episodes felt to have possible or probable IFD using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. There was no difference in 30-day mortality (P=0.21) or 1-year mortality (P=0.57) following introduction of the pathway.Conclusions. Biomarkers can be used safely as part of a multidisciplinary approach to the diagnosis of IFD in neutropaenic haemato-oncology patients. Whilst they do not necessarily result in antifungal therapy being withheld, they can allow more confident diagnosis of IFD and more specific antifungal therapy in selected cases.

Population health outcomes in Nigeria compared with other west African countries, 1998-2019: a systematic analysis for the Global Burden of Disease Study.

BACKGROUND: Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries. METHODS: In this systematic analysis, using data and results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we analysed patterns of mortality, years of life lost (YLLs), years lived with disability (YLDs), life expectancy, healthy life expectancy (HALE), and health system coverage for Nigeria and 15 other west African countries by gender in 1998 and 2019. Estimates of all-age and age-standardised disability-adjusted life-years for 369 diseases and injuries and 87 risk factors are presented for Nigeria. Health expenditure per person and gross domestic product were extracted from the World Bank repository. FINDINGS: Between 1998 and 2019, life expectancy and HALE increased in Nigeria by 18% to 64·3 years (95% uncertainty interval [UI] 62·2-66·6), mortality reduced for all age groups for both male and female individuals, and health expenditure per person increased from the 11th to third highest in west Africa by 2018 (US$18·6 in 2001 to $83·75 in 2018). Nonetheless, relative outcomes remained poor; Nigeria ranked sixth in west Africa for age-standardised mortality, seventh for HALE, tenth for YLLs, 12th for health system coverage, and 14th for YLDs in 2019. Malaria (5176·3 YLLs per 100 000 people, 95% UI 2464·0-9591·1) and neonatal disorders (4818·8 YLLs per 100 000, 3865·9-6064·2) were the leading causes of YLLs in Nigeria in 2019. Nigeria had the fourth-highest under-five mortality rate for male individuals (2491·8 deaths per 100 000, 95% UI 1986·1-3140·1) and female individuals (2117·7 deaths per 100 000, 1756·7-2569·1), but among the lowest mortality for men older than 55 years. There was evidence of a growing non-communicable disease burden facing older Nigerians. INTERPRETATION: Health outcomes remain poor in Nigeria despite higher expenditure since 2001. Better outcomes in countries with equivalent or lower health expenditure suggest health system strengthening and targeted intervention to address unsafe water sources, poor sanitation, malnutrition, and exposure to air pollution could substantially improve population health. FUNDING: The Bill & Melinda Gates Foundation.

Development of a Quality Assurance Score for the Nigeria AIDS Indicator and Impact Survey (NAIIS) Database: Validation Study.

BACKGROUND: In 2018, Nigeria implemented the world's largest HIV survey, the Nigeria AIDS Indicator and Impact Survey (NAIIS), with the overarching goal of obtaining more reliable metrics regarding the national scope of HIV epidemic control in Nigeria. OBJECTIVE: This study aimed to (1) describe the processes involved in the development of a new database evaluation tool (Database Quality Assurance Score [dQAS]) and (2) assess the application of the dQAS in the evaluation and validation of the NAIIS database. METHODS: The dQAS tool was created using an online, electronic Delphi (e-Delphi) methodology with the assistance of expert review panelists. Thematic categories were developed to form superordinate categories that grouped themes together. Subordinate categories were then created that decomposed themes for more specificity. A validation score using dQAS was employed to assess the technical performance of the NAIIS database. RESULTS: The finalized dQAS tool was composed of 34 items, with a total score of 81. The tool had 2 sections: validation item section, which contains 5 subsections, and quality assessment score section, with a score of "1" for "Yes" to indicate that the performance measure item was present and "0" for "No" to indicate that the measure was absent. There were also additional scaling scores ranging from "0" to a maximum of "4" depending on the measure. The NAIIS database achieved 78 out of the maximum total score of 81, yielding an overall technical performance score of 96.3%, which placed it in the highest category denoted as "Exceptional." CONCLUSIONS: This study showed the feasibility of remote internet-based collaboration for the development of dQAS-a tool to assess the validity of a locally created database infrastructure for a resource-limited setting. Using dQAS, the NAIIS database was found to be valid, reliable, and a valuable source of data for future population-based, HIV-related studies.

The Burden of HIV, Hepatitis B and Hepatitis C by Armed Conflict Setting: The Nigeria AIDS Indicator and Impact Survey, 2018.

Background: Against a background of security challenges, Nigeria conducted recently the largest population-based HIV survey in the world to ascertain the burden of the HIV disease in the country. Objective: We evaluated the main outcomes of the survey and the level of success using participation/response indicators. Methods: The survey was conducted from July-December 2018 by over 6,000 field staff across Nigeria in six consecutive webs, using two-stage cluster sampling. We estimated the prevalence of HIV, hepatitis B and hepatitis C in the entire country and by conflict zone status. Adjusted odds ratios (OR) and 95% confidence intervals (CI) from survey logistic regression models were used to compare the likelihood of test positivity for the three infections between zones. Findings: A total of 186,405 adults were interviewed from 97,250 households in 3,848 census enumeration areas. The overall HIV, hepatitis B and hepatitis C positivity rates were 1.55%, 7.63% and 1.73%, respectively. The prevalence of HIV, hepatitis B and C infection was significantly greater in conflict than non-conflict zones (HIV: 1.75% versus 1.0%; hepatitis B: 9.9% versus 7.3%; and hepatitis C: 3.2% versus 0.3%; p < 0.01 in all cases). Individuals living in conflict zones were about three times as likely to test positive for HIV (OR = 2.80, 95% CI = 2.08, 3.60) and nearly six times as likely to test positive for hepatitis C (OR = 5.90, 95% CI = 2.17, 16.67). Conclusion: Large population-based surveys are feasible, even in armed conflict settings. The burden of HIV, hepatitis B and hepatitis C was significantly higher in areas of conflict in Nigeria, highlighting the need for reinforced public health control measures in these settings in order to attain UNAIDS' 95-95-95 targets of controlling the HIV epidemic in sub-Saharan Africa by 2030.

Lessons from co-production of evidence and policy in Nigeria's COVID-19 response.

In February 2020, Nigeria faced a potentially catastrophic COVID-19 outbreak due to multiple introductions, high population density in urban slums, prevalence of other infectious diseases and poor health infrastructure. As in other countries, Nigerian policymakers had to make rapid and consequential decisions with limited understanding of transmission dynamics and the efficacy of available control measures. We present an account of the Nigerian COVID-19 response based on co-production of evidence between political decision-makers, health policymakers and academics from Nigerian and foreign institutions, an approach that allowed a multidisciplinary group to collaborate on issues arising in real time. Key aspects of the process were the central role of policymakers in determining priority areas and the coordination of multiple, sometime conflicting inputs from stakeholders to write briefing papers and inform effective national decision making. However, the co-production approach met with some challenges, including limited transparency, bureaucratic obstacles and an overly epidemiological focus on numbers of cases and deaths, arguably to the detriment of addressing social and economic effects of response measures. Larger systemic obstacles included a complex multitiered health system, fragmented decision-making structures and limited funding for implementation. Going forward, Nigeria should strengthen the integration of the national response within existing health decision bodies and implement strategies to mitigate the social and economic impact, particularly on the poorest Nigerians. The co-production of evidence examining the broader public health impact, with synthesis by multidisciplinary teams, is essential to meeting the social and public health challenges posed by the COVID-19 pandemic in Nigeria and other countries.

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in intensive care.

Introduction. Pneumonia is highly prevalent in intensive care units (ICUs), with high associated mortality. Empirical treatment prioritizes breadth of coverage while awaiting laboratory diagnosis, often at the expense of antimicrobial stewardship. Microarrays use multiple parallel polymerase chain reactions to enable a rapid syndromic approach to laboratory diagnosis.Aim. To evaluate the clinical and laboratory implications of introducing a bespoke 22-pathogen TaqMan Array Card (TAC) for rapid pathogen detection in deep respiratory samples from adult ICUs.Methodology. TAC results from all ICU patients prospectively tested over a 9-month period at Cambridge's Clinical Microbiology and Public Health Laboratory were compared to those of corresponding conventional microbiological assays (culture-, PCR- or serology-based) in terms of result agreement and time-to-result availability. Clinical impact was assessed by retrospective review of medical records.Results. Seventy-one patients were included [45 (63 %) male, median age 59). Overall result agreement was 94 %, with TAC detecting more pathogens than conventional methods. TAC detected Streptococcus pneumoniae more readily than culture (7 vs 0 cases; P=0.02). TAC did not detect Aspergillus spp. in eight culture- or galactomannan-positive cases. The median turnaround time (1 day) was significantly shorter than that of bacterial/fungal culture, Pneumocystis jirovecii PCR and galactomannan testing (each 3 days; P<0.001), atypical bacteria serology (13 days; P<0.001) and Mycobacterium tuberculosis culture (46 days; P<0.001). Earlier result availability prompted discontinuation of unnecessary antimicrobials in 15/71 (21 %) cases, but had no bearing on patient isolation/deisolation.Conclusion. TAC provided greater overall yield of pathogen detection and faster turnaround times, permitting earlier discontinuation of unnecessary antimicrobials.

Verification of HIV Self-Testing Use and Results: A Global Systematic Review.

HIV self-testing (HIVST) allows individuals to interpret and report their own test results, thus decentralizing testing. Yet, this decentralization can make it difficult to verify self-testing results, which is important for linkage to care and surveillance. The aim of this systematic review is to summarize methods for verifying HIVST use and results. We followed guidance from the Cochrane Handbook 5.1 on systematic reviews. We searched four journal databases (PubMed, Embase, Scopus, and Cochrane Library), one clinical trials database (ClinicalTrials.gov), two conference abstract databases (International AIDS Society and Conference on Retroviruses and Opportunistic Infections) and one gray literature database (OpenGrey). We included studies that verified opening of kits or test results. Two researchers independently screened articles and extracted data regarding HIVST location, method of verification, who performed verification, proportion of results verified, and primary or secondary kit distribution. The search yielded 3853 unique citations, of which 40 contained information on HIVST verification and were included. Among these 40 studies, 13 were in high-income countries, 16 were in middle-income countries, and 11 were in low-income countries. Seventeen studies included key populations and two focused on youth. Three methods verified results: supervision by a health provider, returning used test kits, and electronic transmission of photographs. One method verified opening of kits using Bluetooth sensors. Although HIVST has increased worldwide, strategies to verify self-testing results remain limited. These findings suggest a need for additional innovative strategies for verifying HIVST use and results and linkage of self-testing results to surveillance and care systems.

HIV comprehensive knowledge and prevalence among young adolescents in Nigeria: evidence from Akwa Ibom AIDS indicator survey, 2017.

BACKGROUND: Despite the recent increase in HIV infections among adolescents, little is known about their HIV knowledge and perceptions. This study, therefore, sought to examine the factors associated with comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents aged 10-14 years in Akwa Ibom State, Nigeria. Additionally, consenting parents and assenting young adolescents were tested for HIV. METHODS: We used cross-sectional data from the 2017 Akwa Ibom AIDS Indicator Survey to analyze comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents. Demographic characteristics of young adolescents were summarized using descriptive statistics. Chi-square test (or Fisher's exact test in cases of small subgroup sample sizes) was used to elicit associations between demographics and study outcomes. Separate multivariable logistic regression models were then conducted to determine associations with the study outcomes. Sampling weights were calculated in order to adjust for the sample design. P-values less than 0.05 were considered to be significant. RESULTS: A total of 1818 young adolescents were interviewed. The survey highlighted significant low levels of comprehensive HIV knowledge (9.4%) among young adolescents. Adolescent-parent discussions [AOR = 2.19, 95% C.I (1.10-4.38), p = 0.03], schools as sources of HIV information [AOR = 8.06, 95% C.I (1.70-38.33), p < 0.001], and sexual activeness [AOR = 2.55, 95% C.I (1.16-5.60), p = 0.02] were associated with comprehensive HIV knowledge. Majority (93%) of young adolescents perceived themselves not to be at risk of HIV. Overall, 81.5% of young adolescents reported stigmatizing tendencies towards people living with HIV. HIV prevalence among young adolescents was 0.6%. CONCLUSIONS: Results indicate low comprehensive HIV knowledge among young adolescents. Our findings suggest that there is a need for increased attention towards young adolescents particularly in the provision of comprehensive, functional sexuality education, including HIV at the family- and school-levels. Consequently, age appropriate interventions are needed to address the epidemiological risks of young adolescents that are influenced by a myriad of social issues.

Missed opportunities for early infant diagnosis of HIV in rural North-Central Nigeria: A cascade analysis from the INSPIRE MoMent study.

BACKGROUND: Early identification of HIV-infected infants for treatment is critical for survival. Efficient uptake of early infant diagnosis (EID) requires timely presentation of HIV-exposed infants, same-day sample collection, and prompt release of results. The MoMent (Mother Mentor) Nigeria study investigated the impact of structured peer support on EID presentation and maternal retention. This cascade analysis highlights missed opportunities for EID and infant treatment initiation during the study. METHODS: HIV-infected pregnant women and their infants were recruited at 20 rural Primary Healthcare Centers. Routine infant HIV DNA PCR testing was performed at centralized laboratories using dried blood spot (DBS) samples ideally collected by age two months. EID outcomes data were abstracted from study case report forms and facility registers. Descriptive statistics summarized gaps and missed opportunities in the EID cascade. RESULTS: Out of 497 women enrolled, delivery data was available for 445 (90.8%), to whom 415 of 455 (91.2%) infants were live-born. Out of 408 live-born infants with available data, 341 (83.6%) presented for DBS sampling at least once. Only 75.4% (257/341) were sampled, with 81.7% (210/257) sampled at first presentation. Only 199/257 (77.4%) sampled infants had results available up to 28 months post-collection. Two (1.0%) of the 199 infants tested HIV-positive; one infant died before treatment initiation and the other was lost to follow-up. CONCLUSIONS: While nearly 85% of infants presented for sampling, there were multiple missed opportunities, largely due to health system and not necessarily patient-level failures. These included infants presenting without being sampled, presenting multiple times before samples were collected, and getting sampled but results not forthcoming. Finally, neither of the two HIV-positive infants were linked to treatment within the follow-up period, which may have led to the death of one. To facilitate patient compliance and HIV-free infant survival, quality improvement approaches should be optimized for EID commodity availability, consistent DBS sample collection, efficient processing/result release, and prompt infant treatment initiation.

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

Micafungin use in a UK tertiary referral hospital.

OBJECTIVES: Here we sought to describe the real-life usage of micafungin in a UK tertiary referral hospital. METHODS: A prospective, non-interventional, observational surveillance study was performed. RESULTS: Micafungin was commenced in 174 courses involving 148 patients to treat invasive candidiasis and candidaemia (132 courses) and aspergillosis in situations where alternatives such as voriconazole or liposomal amphotericin B could not be used (42 courses). Fungal infection was defined as proven as per European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) guidelines in 84 courses (48.3%). Micafungin was well tolerated; 10 patients (6.8%) developed a rise in alanine aminotransferase (ALT) and only 1 patient stopped therapy due to this. Therapy was rationalised to fluconazole in 77 courses (44.3%). There were no differences in intensive care unit admission or deaths when comparing all 174 courses where patients received micafungin for Aspergillus and Candida infection, respectively [49% vs. 42% (P=0.82) and 24% vs. 15% (P=0.186)]. One patient developed disseminated mucormycosis and four patients had recurrent candidaemia (attributed to poor source control) while receiving micafungin. CONCLUSIONS: Micafungin was clinically effective for the treatment of invasive Candida and Aspergillus infections, and usage did not increase the risk of liver dysfunction even in patients with abnormal ALT at baseline.

The Changing Epidemiology of Invasive Fungal Infections.

Invasive fungal infections (IFI) are an emerging problem worldwide with invasive candidiasis and candidemia responsible for the majority of cases. This is predominantly driven by the widespread adoption of aggressive immunosuppressive therapy among certain patient populations (e.g., chemotherapy, transplants) and the increasing use of invasive devices such as central venous catheters (CVCs). The use of new immune modifying drugs has also opened up an entirely new spectrum of patients at risk of IFIs. While the epidemiology of candida infections has changed in the last decade, with a gradual shift from C. albicans to non-albicans candida (NAC) strains which may be less susceptible to azoles, these changes vary between hospitals and regions depending on the type of population risk factors and antifungal use. In certain parts of the world, the incidence of IFI is strongly linked to the prevalence of other disease conditions and the ecological niche for the organism; for instance cryptococcal and pneumocystis infections are particularly common in areas with a high prevalence of HIV disease. Poorly controlled diabetes is a major risk factor for invasive mould infections. Environmental factors and trauma also play a unique role in the epidemiology of mould infections, with well-described hospital outbreaks linked to the use of contaminated instruments and devices. Blastomycosis is associated with occupational exposure (e.g., forest rangers) and recreational activities (e.g., camping and fishing).The true burden of IFI is probably an underestimate because of the absence of reliable diagnostics and lack of universal application. For example, the sensitivity of most blood culture systems for detecting candida is typically 50 %. The advent of new technology including molecular techniques such as 18S ribosomal RNA PCR and genome sequencing is leading to an improved understanding of the epidemiology of the less common mould and dimorphic fungal infections. Molecular techniques are also providing a platform for improved diagnosis and management of IFI.Many factors affect mortality in IFI, not least the underlying medical condition, choice of therapy, and the ability to achieve early source control. For instance, mortality due to pneumocystis pneumonia in HIV-seronegative individuals is now higher than in seropositive patients. Of significant concern is the progressive increase in resistance to azoles and echinocandins among candida isolates, which appears to worsen the already significant mortality associated with invasive candidiasis. Mortality with mould infections approaches 50 % in most studies and varies depending on the site, underlying disease and the use of antifungal agents such as echinocandins and voriconazole. Nevertheless, mortality for most IFIs has generally fallen with advances in medical technology, improved care of CVCs, improved diagnostics, and more effective preemptive therapy and prophylaxis.

Patient and public understanding and knowledge of antimicrobial resistance and stewardship in a UK hospital: should public campaigns change focus?

BACKGROUND: The rising global tide of antimicrobial resistance is a well-described phenomenon. Employing effective and innovative antimicrobial stewardship strategies is an essential approach to combat this public health threat. Education of the public and patients is paramount to enable the success of such strategies. METHODS: A panel of hospital multidisciplinary healthcare professionals was set up and a short quiz containing true/false statements around antimicrobial stewardship and resistance was designed and piloted. An educational leaflet with the correct replies and supporting information was also produced and disseminated. Participants were recruited on a single day (18 November 2015) from the hospital outpatient clinics and the hospital outpatient pharmacy waiting room. RESULTS: One hundred and forty-five completed quizzes were returned, providing a total of 1450 answers. Overall, 934 of 1450 (64%) statements were scored correctly whilst 481 (33%) were scored incorrectly; 35 (3%) statements were left unscored. We speculate that these results may demonstrate that respondents understood the statements, as only a small proportion of statements were left unanswered. The question dealing with the definition of antimicrobial resistance and the question dealing with the definition of antimicrobial stewardship obtained the most incorrect replies (85% and 72%, respectively). However, a specific factual recall question regarding only one microorganism (MRSA) received the most correct responses (99%). CONCLUSIONS: We describe a simple, innovative method of engagement with patients and the general public to help educate and disseminate important public health messages around antimicrobial resistance and stewardship. We also identified the need for public health campaigns to address the knowledge gaps found around this topic.

Vancomycin resistant enterococci in urine cultures: Antibiotic susceptibility trends over a decade at a tertiary hospital in the United Kingdom.

PURPOSE: Enterococci are a common cause of urinary tract infection and vancomycin-resistant strains are more difficult to treat. The purpose of this surveillance program was to assess the prevalence of and determine the risk factors for vancomycin resistance in adults among urinary isolates of Enterococcus sp. and to detail the antibiotic susceptibility profile, which can be used to guide empirical treatment. MATERIALS AND METHODS: From 2005 to 2014 we retrospectively reviewed 5,528 positive Enterococcus sp. urine cultures recorded in a computerized laboratory results database at a tertiary teaching hospital in Cambridge, United Kingdom. RESULTS: Of these cultures, 542 (9.8%) were vancomycin resistant. No longitudinal trend was observed in the proportion of vancomycin-resistant strains over the course of the study. We observed emerging resistance to nitrofurantoin with rates climbing from near zero to 40%. Ampicillin resistance fluctuated between 50% and 90%. Low resistance was observed for linezolid and quinupristin/dalfopristin. Female sex and inpatient status were identified as risk factors for vancomycin resistance. CONCLUSIONS: The incidence of vancomycin resistance among urinary isolates was stable over the last decade. Although resistance to nitrofurantoin has increased, it still serves as an appropriate first choice in uncomplicated urinary tract infection caused by vancomycin-resistant Enterococcus sp.