Elizabeth Haworth

Viral respiratory infections at the Hajj: comparison between UK and Saudi pilgrims

ABSTRACT A high incidence of respiratory infection, including influenza, has been reported at the Hajj in Mecca, Saudi Arabia. Reported rates of influenza have been higher among UK than among domestic pilgrims, but this could be explained by methodological differences among studies. Accordingly, the present study compared the frequencies of respiratory viruses among UK and Saudi pilgrims using the same study design. Pilgrims with upper respiratory tract symptoms were recruited from Mecca and the neighbouring valley Mina during the Hajj 2006. Nasal swabs were used for point-of-care influenza testing and real-time RT-PCR (rtRT-PCR) tests for influenza virus, rhinovirus, parainfluenza virus, adenovirus, human metapneumovirus and respiratory syncytial virus. Of 260 pilgrims investigated, 150 were from the UK and 110 were Saudi; of these, 38 (25%) UK pilgrims and 14 (13%) Saudi pilgrims had respiratory infections detectable by rtRT-PCR (p 0.01). In the UK group, there were 19 (13%) cases of rhinovirus infection, 15 (10%) cases of influenza virus infection, two (1%) cases of dual infections with influenza virus and rhinovirus, one (3%) case of parainfluenza virus infection, and one (1%) case of respiratory syncytial virus infection. Fifty-six (37%) UK pilgrims had been vaccinated against influenza virus, with the rates of influenza in the vaccinated and unvaccinated group being 7% and 14%, respectively (p 0.19). In the Saudi group, there were three (3%) cases of rhinovirus infection and 11 (10%) cases of influenza. Only four (4%) Saudi pilgrims had been vaccinated against influenza virus, and none of these was infected with influenza virus. Overall, a significantly higher proportion of the UK pilgrims had detectable respiratory infections (25% vs. 13%, p 0.01). Influenza rates were similar in both groups, but the reported rates of influenza vaccination differed.

Influenza and respiratory syncytial virus infections in British Hajj pilgrims

Viral respiratory infections including influenza and respiratory syncytial virus (RSV) have been reported during the Hajj among international pilgrims. To help establish the burden of these infections at the Hajj, we set up a study to confirm these diagnoses in symptomatic British pilgrims who attended the 2005 Hajj. UK pilgrims with symptoms of upper respiratory tract infection (URTI) were invited to participate; after taking medical history, nasal swabs were collected for point-of-care testing (PoCT) of influenza and for subsequent PCR analysis for influenza and RSV. Of the 205 patients recruited, 37 (18%) were positive for either influenza or RSV. Influenza A (H3) accounted for 54% (20/37) of the virus-positive samples, followed by RSV 24% (9/37), influenza B 19% (7/37), and influenza A (H1) 3% (1/37). Of the influenza-positive cases, 29% (8/28) had recently had a flu immunisation. Influenza was more common in those who gave a history of contact with a pilgrim with a respiratory illness than those who did not (17 versus 9%). The overall rate of RSV was 4% (9/202). This study confirms that influenza and RSV cause acute respiratory infections in British Hajj pilgrims. Continuing surveillance and a programme of interventions to contain the spread of infection are needed at the Hajj, particularly when the world is preparing for an influenza pandemic.

Invasive pneumococcal disease : epidemiology in children and adults prior to implementation of the conjugate vaccine in the Oxfordshire region, England

A 10-year invasive pneumococcal disease (IPD) enhanced surveillance project in the Oxfordshire region of the UK between 1996 and 2005 identified a total of 2691 Streptococcus pneumoniae isolates from all ages that provided a comprehensive description of pneumococcal epidemiology. All isolates were serotyped and those from children under 5 years of age were genotyped and a matched case-control study using adults hospitalized between 1995 and 2000 was performed to estimate the effectiveness of the pneumococcal polysaccharide vaccine in the local population. Fifty-one serotypes were isolated, with different age distributions. The overall incidence of IPD was 9.2 cases per 100 000 population per annum [95 % confidence interval (CI), 8.6-9.9] and that of meningitis was 0.7 per 100 000 population per annum (95 % CI 0.5-0.9). After adjusting for age, serotype 1 was found to be less likely to be associated with meningitis versus other IPD, compared with the most common serotype 14, whereas serotype 12F was more likely to cause meningitis than other IPD. There were significant temporal changes in IPD incidence of four serotypes, with decreases in serotypes 1, 12F and 14 and increases in serotype 8. A possible novel variant (from serotype 6A to 6B) was found using multilocus sequence typing analysis. From the matched case-control study of adults, the pneumococcal polysaccharide vaccine effectiveness was estimated to be 43 % (2-68 %), which did not change significantly after adjustment for pre-existing co-morbidities. The data provide a baseline against which the impact of the pneumococcal conjugate vaccine introduced in the UK in 2006 could be measured.

Prevention of influenza at Hajj: applications for mass gatherings

Summary Outbreaks of infectious diseases that spread via respiratory route, e.g. influenza, are common amongst Hajj congregation in Mecca, Saudi Arabia. The Saudi Arabian authority successfully organized the Hajj 2009 amidst fear of pandemic influenza. While severe influenza A(H1N1)pdm09 was rare, the true burden of pandemic influenza at Hajj that year remains speculative. In this article we review the latest evidence on influenza control and discuss our experience of influenza and its prevention at Hajj and possible application to other mass gatherings. Depending on study design the attack rate of seasonal influenza at Hajj has ranged from 6% in polymerase chain reaction or culture confirmed studies to 38% in serological surveillance. No significant effect of influenza vaccine or the use of personal protective measures against influenza has been established from observational studies, although the uptake of the vaccine and adherence to face masks and hand hygiene has been low. In all, there is a relatively poor evidence base for control of influenza. Until better evidence is obtained, vaccination coupled with rapid antiviral treatment of symptomatic individuals remains the mainstay of prevention at Hajj and other mass gatherings. Hajj pilgrimage provides a unique opportunity to test the effectiveness of various preventive measures that require a large sample size, such as testing the efficacy of plain surgical masks against laboratory-confirmed influenza. After successful completion of a pilot trial conducted among Australian pilgrims at the 2011 Hajj, a large multinational cluster randomized controlled trial is being planned. This will require effective international collaboration.

Hazards of hepatitis at the Hajj

While an increased risk of hepatitis is associated with travel, the risk of hepatitis associated with the Islamic Hajj pilgrimage to Mecca, Saudi Arabia has not been carefully quantified. Conditions unique to this gathering can pose the risk of both enteral and parenteral viral hepatitis. During this congregation, pilgrims stay in tents shared by 100 or more people often living on foods from street vendors and sharing common toilet facilities that can expose them to both hepatitis A and E. To mark the end of the festival, head shaving or trimming by fellow pilgrims or street barbers, who often re-use their razor may expose them to hepatitis B or C. Pilgrims are also at risk of cuts to the hands and feet while sacrificing cattle and walking barefooted, which may further increase the risk of parenteral viral hepatitis. Emerging diseases such as Alkhumra virus and Rift Valley fever, which may cause hepatitis, are also potentially important for the Hajj pilgrims. Improved health education to increase awareness about the risk of these diseases and appropriate immunisations, particularly hepatitis A and B vaccines, could play an important role.

Influenza vaccine uptake among British Muslims attending Hajj, 2005 and 2006

Every year 1% of British Muslims travel to Saudi Arabia on the Hajj pilgrimage. High rates of influenza have been reported among pilgrims,1 2 and the Saudi Arabian Ministry of Health recommends that all pilgrims should receive influenza vaccination before travelling. We determined the uptake of influenza vaccination among British Hajj pilgrims who attended the British Hajj Delegation Clinic in Mecca and mobile clinics set up by us in Mina in 2005 and 2006. In 2005, 196 pilgrims were recruited and in 2006, 146 (age …

Influenza and meningococcal disease: Lessons for travellers and government from 2 epidemic diseases

Influenza and meningococcal disease are two serious diseases that are especially linked. Outbreaks of influenza have been frequently associated with secondary outbreaks of meningococcal disease. Travellers such as Hajj pilgrims are at particular risk, the most recent meningococcal outbreaks being in 2000 and 2001, while concern is rising that the annual pilgrimage, centred as it presently is on winter, may even become the epicentre of an avian influenza pandemic. Routine vaccination of pilgrims against meningococcal disease using a 4-valent product has been in place since 2002 with good effect, but influenza vaccine is not yet routinely required for all pilgrims despite the high proportion afflicted. Meningococcal polysaccharide vaccines are effective in older children and adults and this cheaper product can play a role in the short term management of meningococcal outbreaks due to serogroups A, C, W135 or Y. The impressively fast development of a C conjugate vaccine in the late 1990s was a credit to the close collaboration of pharma, academia and the executive. A similar alignment could accelerate the production of an efficacious and cost-effective H5N1 influenza vaccine through direct transparent competition with head-to-head randomised, double-blinded controlled trials. Both organisms have a propensity to mutate and adapt to immune pressure. There are lessons to be learnt from how we manage each for the control of the other.

Unmasking Masks in Makkah: Preventing Influenza at Hajj

Each year more than 2 million people from all over the world attend the Hajj pilgrimage to Saudi Arabia. At least 60% of them develop respiratory symptoms there or during outward or homebound transit [1, 2]. During recent interpandemic years, approximately 1 in 10 pilgrims with respiratory symptoms in Makkah have had influenza detected by polymerase chain reaction tests of respiratory samples [3, 4]. Pneumonia is the leading cause of hospitalization at Hajj, accounting for approximately 20% of diagnoses on admission [5]. Hajj 2009 took place in November in the middle of the influenza A H1N1 pandemic (pH1N1). However, a recent report suggests that the prevalence of pH1N1 was 0.2% (n 5 1) among 519 arriving pilgrims and 0.1% (n 5 2) among 2699 departing pilgrims [6], probably because of heightened infection control and preexisting crossimmunity among pilgrims, most of whom would have been exposed to H1N1 before 1957 [7]. Experience from an ear, nose, and throat (ENT) clinic in Makkah suggested that only 77 of 3087 patients (2.5%) who attended with ENT symptoms had suspected pH1N1 based on history of contact with a patient with pH1N1 and clinical symptoms of influenza-like illness (ILI); however, laboratory testing for influenza virus was not undertaken [8]. The efficacy of influenza vaccine is dependent on matching the vaccine and circulating influenza strains. Because the pH1N1 vaccine was not largely available in time for Hajj 2009, protection was dependent on previous exposure to H1N1 influenza A virus and nonpharmaceutical interventions such as face masks [2]. Historically, face masks have been used to prevent or reduce nosocomial transmission of pandemic influenza since, at least, the time of Spanish influenza in 1918. Nurses who wore specially designed face masks and changed them every 2 hours experienced lower infection rates than those who did not [9]. Recent experiments confirm that surgical masks and respirators can filter influenza virus, although observational studies or clinical trials have not yet clearly demonstrated the effectiveness of plain surgical masks in household or healthcare settings [10–16]. The role of surgical masks, respirators, and/or hand hygiene in preventing ILI has been examined in at least 15 studies including 5 randomized controlled trials (RCTs). These compared ‘‘plain surgical mask’’ with ‘‘no intervention’’ against ILI [10–14]. In 4 of these RCTs influenza was laboratory confirmed [10–13]. Metadata from these studies indicated that wearing surgical masks did not change the frequency of laboratoryconfirmed influenza (Figure 1). The findings may have been due to limitations and biases in study design [10– 14]. A common limitation of all studies was small sample size. Despite similar study design, the sample-size calculations were based on different assumptions, and the studies lacked the power to detect a difference in incidence of laboratoryconfirmed influenza. At least 2 observational studies at the Hajj have examined the role of masks in preventing acute respiratory infection. One of these studies evaluated the role of face masks among pilgrims at the 2002 Hajj [15], when a protective effect was shown in men but not in women. The other study evaluated the use of face masks worn by healthcare workers at the 2005 Hajj in preventing acquisition of acute respiratory infection when protective effectiveness was nonsignificant [16]. The Hajj congregation of more than 2 million people who stay for 5 days in 25 000 tents in Mina, a valley within Makkah city, provides a unique opportunity to conduct RCTs of mask effectiveness to avoid sample size and design limitations. During Hajj 2011 the 5-day stay in Mina is from 4 to 8 November. We are undertaking a pilot study to examine the feasibility of a cluster RCT of mask use among Australian pilgrims. Assuming success of this pilot trial, we plan to set up large RCT involving pilgrims from several countries in subsequent years. We are seeking expressions of interest for a multinational collaboration and would be pleased to hear from possible collaborators.

Conjugate versus polysaccharide meningococcal vaccine

Caroline Trotter and Brian Greenwood highlighted that only one of six studies that investigated the eff ect of a monovalent or bivalent meningococcal polysaccharide vaccine on pharyngeal carriage in Africa reported a signifi cant eff ect. So far, no African study we are aware of has investigated the eff ect of meningococcal conjugate vaccine on pharyngeal carriage. However, a systematic review of 29 published papers has shown that one study involving meningococcal serogroup C conjugate vaccine found a “marked and highly statistically signifi cant” decrease in carriage, whereas those involving polysaccharide vaccine found no signifi cant eff ect of the vaccine on carriage status. This fi nding is consistent with the eff ect of other conjugate vaccines, such as those for pneumococcus and Haemophilus infl uenzae type b, where glycoconjugation to a protein carrier improves mucosal immunity through a T-cell-mediated immune response. Since more than half of the 300 million population within the meningitis belt are Muslims, it is conceivable that because of the Hajj pilgrimage, the region has played a crucial part in the global spread of meningococcus W135 during this decade. Although pilgrims are required to have a tetravalent (polysaccharide or conjugate) meningococcal vaccine against serotypes A, C, Y, and W135 as a prerequisite for the Hajj visa, a recent survey shows that over a third of the local pilgrims remain unvaccinated. It is possible that further outbreaks will occur if the transmission chain is not broken by proper eradication of carriage. Apart from countries in North America, most nations that send pilgrims to the Hajj still use a tetravalent polysaccharide vaccine, which is less likely to reduce carriage status compared with a conjugate one. We recommend that a conjugate vaccine rather than a polysaccharide tetravalent meningococcal vaccine is used for Hajj pilgrims as soon as possible. Mandatory conjugate vaccine should make unnecessary the chemoprophylaxis programme currently practised at entry points in Saudi Arabia, which targets all pilgrims arriving from the African meningitis belt. However, a proper carriage study is likely to be necessary to support this policy change.

Immunogenicity of routine vaccination against diphtheria, tetanus, and Haemophilus influenzae type b in Asian infants born in the United Kingdom

Aim: To determine the immunogenicity of routine vaccination against diphtheria, tetanus, and Haemophilus influenzae type b (Hib) in Asian infants born in the UK, and whether maternal antibody suppression occurs. Methods: A cohort study with 80% power, within 95% confidence limits, to show that 80% or fewer Asian infants would respond with an anti-PRP antibody concentration >0.15 μg/ml. Infants of South Asian origin born in Berkshire were enrolled at two general practices in Reading: 41 Asian families sequentially asked to participate within 2 weeks of birth; 36 infants were enrolled and 34 completed the study. Main outcome measures were: antibody concentration against diphtheria, tetanus, and Hib expressed as geometric mean titres (GMT) and proportion of infants about a threshold protective antibody concentration. Results: Median age for completing primary vaccination course was 5 months. All 34 achieved anti-PRP antibody concentration of >0.15 μg/ml, 33 were >1.0 μg/ml, and the GMT was 15.0 μg/ml. All infants developed protective antibody concentration >0.1 IU/ml for tetanus and diphtheria; the respective GMTs were 1.94 and 5.57 IU/ml. Infants with high (>0.25 IU/ml) antibody concentrations against diphtheria and tetanus at 2 months achieved lower antibody concentrations after their three dose course than those with low concentrations (<0.1 IU/ml) (p = 0.06 and 0.03, respectively). Conclusions: Despite evidence for maternal antibody suppression of the response to tetanus and diphtheria vaccination, excellent antibody responses were achieved by routine vaccination according to the accelerated schedule. High vaccine coverage should be encouraged to provide protection against the possibility of imported infection.