Hamish Mohammed

Transcriptomic Profiling of Diverse Aedes aegypti Strains Reveals Increased Basal-level Immune Activation in Dengue Virus-refractory Populations and Identifies Novel Virus-vector Molecular Interactions

Genetic variation among Aedes aegypti populations can greatly influence their vector competence for human pathogens such as the dengue virus (DENV). While intra-species transcriptome differences remain relatively unstudied when compared to coding sequence polymorphisms, they also affect numerous aspects of mosquito biology. Comparative molecular profiling of mosquito strain transcriptomes can therefore provide valuable insight into the regulation of vector competence. We established a panel of A. aegypti strains with varying levels of susceptibility to DENV, comprising both laboratory-maintained strains and field-derived colonies collected from geographically distinct dengue-endemic regions spanning South America, the Caribbean, and Southeast Asia. A comparative genome-wide gene expression microarray-based analysis revealed higher basal levels of numerous immunity-related gene transcripts in DENV-refractory mosquito strains than in susceptible strains, and RNA interference assays further showed different degrees of immune pathway contribution to refractoriness in different strains. By correlating transcript abundance patterns with DENV susceptibility across our panel, we also identified new candidate modulators of DENV infection in the mosquito, and we provide functional evidence for two potential DENV host factors and one potential restriction factor. Our comparative transcriptome dataset thus not only provides valuable information about immune gene regulation and usage in natural refractoriness of mosquito populations to dengue virus but also allows us to identify new molecular interactions between the virus and its mosquito vector.

Improving surveillance of sexually transmitted infections using mandatory electronic clinical reporting: the genitourinary medicine clinic activity dataset, England, 2009 to 2013

A new electronic surveillance system for sexually transmitted infections (STIs) was introduced in England in 2009. The genitourinary medicine clinic activity dataset (GUMCAD) is a mandatory, disaggregated, pseudo-anonymised data return submitted by all STI clinics across England. The dataset includes information on all STI diagnoses made and services provided alongside demographic characteristics for every patient attendance at a clinic. The new system enables the timely analysis and publication of routine STI data, detailed analyses of risk groups and longitudinal analyses of clinic attendees. The system offers flexibility so new codes can be introduced to help monitor outbreaks or unusual STI activity. From January 2009 to December 2013 inclusive, over twenty-five million records from a total of 6,668,648 patients of STI clinics have been submitted. This article describes the successful implementation of this new surveillance system and the types of epidemiological outputs and analyses that GUMCAD enables. The challenges faced are discussed and forthcoming developments in STI surveillance in England are described.

Increase in Sexually Transmitted Infections among Men Who Have Sex with Men, England, 2014.

Surveillance data from sexual health clinics indicate recent increases in sexually transmitted infections, particularly among men who have sex with men. The largest annual increase in syphilis diagnoses in a decade was reported in 2014. Less condom use may be the primary reason for these increases.

Fall in new HIV diagnoses among men who have sex with men (MSM) at selected London sexual health clinics since early 2015: testing or treatment or pre-exposure prophylaxis (PrEP)?

Since October 2015 up to September 2016, HIV diagnoses fell by 32% compared with October 2014–September 2015 among men who have sex with men (MSM) attending selected London sexual health clinics. This coincided with high HIV testing volumes and rapid initiation of treatment on diagnosis. The fall was most apparent in new HIV testers. Intensified testing of high-risk populations, combined with immediately received anti-retroviral therapy and a pre-exposure prophylaxis (PrEP) programme, may make elimination of HIV achievable.

Contribution of transmission in HIV-positive men who have sex with men to evolving epidemics of sexually transmitted infections in England: an analysis using multiple data sources, 2009-2013.

HIV seroadaptive behaviours may have contributed to greater sexually transmitted infection (STI) transmission in HIV-positive men who have sex with men(MSM) and to the global increase in STIs. Using multiple national surveillance data sources and population survey data, we estimated the risk of STIs in HIV-positive MSM and assessed whether transmission in HIV-positive MSM has contributed to recent STI epidemics in England. Since 2009, an increasing proportion of STIs has been diagnosed in HIV-positive MSM, and currently, the population rate of acute bacterial STIs is up to four times that of HIV-negative or undiagnosed MSM. Almost one in five of all diagnosed HIV-positive MSM in England had an acute STI diagnosed in 2013. From 2009 to 2013, the odds of being diagnosed with syphilis increased from 2.71 (95% confidence interval (CI) 2.41–3.05, p<0.001) to 4.05 (95%CI 3.70-4.45, p<0.001) in HIV-positive relative to HIV negative/undiagnosed MSM. Similar trends were seen for gonorrhoea and chlamydia. Bacterial STI re-infection rates were considerably higher in HIV-positive MSM over a five-year follow-up period, indicative of rapid transmission in more dense sexual networks.These findings strongly suggest that the sexual health of HIV-positive MSM in England is worsening, which merits augmented public health interventions and continued monitoring.

Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases.

Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson’s χ2 and student’s t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson’s χ2 and Fisher’s exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28–16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever—aOR: 0.56 [0.40–0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71–0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which can be used to triage patients for appropriate care in the clinical setting.

Diagnosis and treatment of chlamydia and gonorrhoea in general practice in England 2000–2011: a population-based study using data from the UK Clinical Practice Research Datalink

Objectives To determine the relative contribution of general practices (GPs) to the diagnosis of chlamydia and gonorrhoea in England and whether treatment complied with national guidelines. Design Analysis of longitudinal electronic health records in the Clinical Practice Research Datalink (CPRD) and national sexually transmitted infection (STI) surveillance databases, England, 2000–2011. Setting GPs, and community and specialist STI services. Participants Patients diagnosed with chlamydia (n=1 386 169) and gonorrhoea (n=232 720) at CPRD GPs, and community and specialist STI Services from 2000–2011. Main outcome measures Numbers and rates of chlamydia and gonorrhoea diagnoses; percentages of patients diagnosed by GPs relative to other services; percentage of GP patients treated and antimicrobials used; percentage of GP patients referred. Results The diagnosis rate (95% CI) per 100 000 population of chlamydia in GP increased from 22.8 (22.4–23.2) in 2000 to 29.3 (28.8–29.7) in 2011 (p<0.001), while the proportion treated increased from 59.5% to 78.4% (p=0.001). Over 90% were prescribed a recommended antimicrobial. Over the same period, the diagnosis rate (95% CI) per 100 000 population of gonorrhoea in GP ranged between 3.2 (3–3.3) and 2.4 (2.2–2.5; p=0.607), and the proportion treated ranged between 32.7% and 53.6% (p=0.262). Despite being discontinued as a recommended therapy for gonorrhoea in 2005, ciprofloxacin accounted for 42% of prescriptions in 2007 and 20% in 2011. Over the study period, GPs diagnosed between 9% and 16% of chlamydia cases and between 6% and 9% of gonorrhoea cases in England. Conclusions GP makes an important contribution to the diagnosis and treatment of bacterial STIs in England. While most patients diagnosed with chlamydia were managed appropriately, many of those treated for gonorrhoea received antimicrobials no longer recommended for use. Given the global threat of antimicrobial resistance, GPs should remain abreast of national treatment guidelines and alert to treatment failure in their patients.

Risk Factors of Porcine Cysticercosis in the Eastern Cape Province, South Africa

There is a high prevalence of Taenia solium taeniosis/cysticercosis in humans and pigs in the Eastern Cape Province (ECP) of South Africa. The objective of this study was to identify risk factors of porcine cysticercosis in select districts of the ECP. Data were collected in 2003 by interviewing 217 pig producers from the area. Blood samples were collected from 261 of their pigs, which were tested using two enzyme-linked immunosorbent assays (ELISA) for the presence of antibodies to cysticercosis. Frequencies of both owner- and pig-level characteristics were determined. For pig-level analysis, all bivariable and multivariable associations were determined using the surveylogistic procedure of the SAS/STAT® software to accommodate for the intraclass correlation that exists for clusters of pigs within one owner and for clusters of owners within a district. All tests for significance were performed at the α = 0.05 level, and adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined. Among the respondents, 48% of their households lacked a latrine, 98% slaughtered pigs at home, and 99% indicated that meat inspection services were not available. On bivariable analysis, there was a significant association between porcine infection and district (p = 0.003), breed (p = 0.041) and the absence of a latrine (p = 0.006). On multivariable analysis, the absence of a latrine was the only variable significantly associated with porcine infection (aOR = 1.89; 95% CI = 1.07, 3.35) (p = 0.028). The increased odds of porcine infection with households lacking a latrine contributes to our understanding of the transmission of this parasite in the ECP. Determining and addressing the risk factors for T. solium infection can potentially lower the very high prevalence in humans and pigs in this endemic area.

Sexualised drug use in people attending sexual health clinics in England

Recent evidence highlights an increase in ‘chemsex’, the use of recreational drugs during sex, in men who have sex with men (MSM) and an association with risky sexual behaviours and outbreaks of STIs.1 However, the extent of sexualised drug use in people attending sexual health clinics (SHCs) is unknown. STI surveillance in England is performed by Public Health England (PHE) using a disaggregated patient-level dataset of all diagnoses and services at SHCs.2 This is a minimum dataset with key demographic and clinical variables, but lacks behavioural data. To address this gap, PHE …

Sequelae and Other Conditions in Ebola Virus Disease Survivors, Sierra Leone, 2015

We rapidly assessed the health of Ebola virus disease (EVD) survivors in Kenema, Sierra Leone, by reviewing medical charts of all patients attending the Survivor Clinic of Kenema Government Hospital. Data were abstracted on signs and symptoms at every attendance. As of November 2015, a total of 621 attendances by 115 survivors with laboratory-confirmed EVD were made to the Survivor Clinic. Most (60.9%) survivors were women. Survivors’ median age was 28 years (range 0.25–70 years). Survivors attended the clinic a median of 5 times (range 1–21 times) each, and the median time from EVD discharge to attendance was 261 days (range 4–504 days). The most commonly reported signs and symptoms among the 621 attendances were headache (63.1%), fever (61.7%), and myalgia (43.3%). Because health needs of EVD survivors are complex, rapid chart reviews at survivor clinics should be repeated regularly to assess the extent of illness and prioritize service delivery.