Active screening and surveillance in the United Kingdom for Middle East respiratory syndrome coronavirus in returning travellers and pilgrims from the Middle East: a prospective descriptive study for the period 2013-2015.

BACKGROUND: Over 25000 pilgrims from the UK visit Saudi Arabia every year for the Umrah and Hajj pilgrimages. The recent outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in South Korea and the continuing reports of MERS-CoV cases from Saudi Arabia highlight the need for active surveillance for MERS-CoV in returning pilgrims or travellers from the Middle East. Public Health England Birmingham Laboratory (PHEBL) is one of a few selected UK public health laboratories responsible for MERS-CoV screening in travellers returning to the UK from the Middle East who present to hospital with severe respiratory symptoms. The results of the PHEBL MERS-CoV screening and surveillance over the past 3 years is presented. METHODS: UK travellers/pilgrims who returned from the Middle East and presented to a hospital with respiratory symptoms were studied over the period February 1, 2013 to December 31, 2015. Patients with respiratory symptoms, who satisfied the Public Health England MERS-CoV case algorithm, were tested for MERS-CoV and other respiratory tract viruses on admission to hospital. RESULTS: Two hundred and two patients suspected of having MERS-CoV were tested. None of them had a laboratory-confirmed MERS-CoV infection. A viral aetiology was detected in half (50.3%) of the cases, with rhinoviruses, influenza A (H1N1 and H3N2), and influenza B being most frequent. Peak testing occurred following the annual Hajj season and in other periods of raised national awareness. CONCLUSIONS: Respiratory tract infections in travellers/pilgrims returning to the UK from the Middle East are mainly due to rhinoviruses, influenza A, and influenza B. Whilst MERS-CoV was not detected in the 202 patients studied, heightened awareness of the possibility of MERS-CoV and continuous proactive surveillance are essential to rapidly identify cases of MERS-CoV and other seasonal respiratory tract viruses such as avian influenza, in patients presenting to hospital. Early identification and isolation may prevent outbreaks in nosocomial settings.

Does genotype predict response to treatment in children infected with hepatitis B perinatally?

HBV genotype may correlate with outcome and treatment response. Genotype has been compared with treatment response in children infected perinatally with hepatitis B following treatment with oral antiviral drugs (lamivudine or adefovir) or interferon (IFN) alone and with prednisolone priming (Pred/IFN). All children who took part in clinical trials in this unit since 1990 were included. Hepatitis B genotypes were determined by direct sequencing or using a commercial line probe assay (InnoLipa). Sixty-five children were included; 20 were treated with IFN; 19 with Pred/IFN; 22 with lamivudine and 7 with adefovir, some took part in more than one treatment study. 63 out of 65 children were clearly typed into single genotypes; 16, 7, 3, and 37 typing as A, B, C, and D respectively. The majority of South-Asian children had genotype D and European and Afro-Caribbean children were more likely to have genotype A. Treatment response (seroconversion from HBeAg to Anti-HBe) was better in children with genotypes A [n = 16] and D [n = 37] (55.5% and 48.7%), compared to those with B [n = 7] and C [n = 3] (12.5% and 0%) for all treatments. The response to interferon alone was better in children with genotype A compared to D (50% and 36%), but prednisolone priming improved the response so that there was no difference between genotypes A and D (66.7% and 70%). Assessment of genotype in children pre-treatment may provide a guide to potential response. The response to treatment by genotype should be evaluated in future clinical trials in children.

Dynamics of raltegravir resistance profile in an HIV type 2-infected patient.

The evolutionary dynamics of RAL resistance in the HIV-2 virus were examined through population and clonal sequence analysis of the IN from baseline, during treatment, and after stopping RAL therapy. The treatment failure of an RAL regimen in the HIV-2 patient studied was associated with the emergence of mutations via the N155H resistance pathway and subsequent switching to the Y143C mutational route. This study has also identified four novel secondary mutations, Q91R, S147G, A153G, and M183I, not previously reported in HIV-1 patients failing RAL therapy. Resistant variants involving the Y143C pathway were noted to have persisted beyond 4 weeks following the cessation of RAL therapy. All resistance-associated mutations were lost at 20 weeks after stopping RAL therapy. Our findings provide evidence supporting the supposition that substantial cross-resistance between strand transfer IN-Is is likely in HIV-2 as shown in HIV-1.

Drug-resistant HIV-1 in the semen of men receiving antiretroviral therapy with acute sexually transmitted infections.

Sexually transmitted infections may enhance the sexual transmission of HIV-1. It is possible that loss of virological control in patients with such infections receiving antiretroviral therapy (ART) may even facilitate the transmission of drug-resistant HIV. We have recently demonstrated that in those on maximally suppressive ART this effect is reduced. We have examined the virus obtained from the blood plasma and seminal plasma of six HIV-1-infected men receiving poorly suppressive ART with acute urethritis for the presence of drug resistance-associated mutations. In four men with gonorrhoea the blood and seminal plasma HIV-1 had mutations conferring reduced susceptibility to one or more available drugs. In one of these men the viral load of drug-resistant virus in seminal plasma was 20-fold higher during gonorrhoea than following antibiotic treatment, with no change in blood plasma viral load. We conclude that in the presence of suboptimal ART, sexually transmitted infections may enhance the spread of drug-resistant HIV-1.

Identification of a transmission chain of HIV type 1 containing drug resistance-associated mutations.

We have investigated a potential transmission chain of HIV-1 with drug resistance-associated mutations between three individuals over a period of 5 years by use of cloning and sequencing of viral genes, and phenotypic characterization. Viruses containing reverse transcriptase drug resistance-associated mutations were transmitted sequentially between three homosexual men (A, B, and C), and persisted in one individual for at least 4 years, despite intermittent therapy and reduced viral replicative capacity compared with wild-type strains. Clonal analysis of the envelope gene from semen and blood virus showed that the virus transmitted to patient C was more closely related to virus from the semen than the blood of patient B. Our data suggest that HIV variants with drug resistance-associated mutations can persist following primary infection, despite intervening antiretroviral therapy, and subsequently sexually transmitted. We provide "proof of principle" that such mutations can therefore become "fixed" within the circulating virus pool.

Minimal variation in T-20 binding domain of different HIV-1 subtypes from antiretroviral-naive and -experienced patients.

In-vitro differences in T-20 susceptibility among HIV-1 subtypes have been reported. We therefore studied the T-20 binding domain of a variety of virus subtypes from both antiretroviral-naive and -experienced patients. Minimal variation in the HR-1 region of gp41 was observed, especially within the region responsible for T-20 resistance. Any subtype differences in T-20 susceptibility do not appear to be related to HR-1 genetic variation.