WHO recommends that 70% of dogs in a population should be immunized to eliminate or prevent outbreaks of rabies. This critical percentage (pc) has been established empirically from observations on the relationship between vaccination coverage and rabies incidence in dog populations around the world. Here, by contrast, we estimate pc by using epidemic theory, together with data available from four outbreaks in urban and rural areas of the USA, Mexico, Malaysia and Indonesia. From the rate of increase of cases at the beginning of these epidemics, we obtain estimates of the basic case reproduction number of infection, R0, in the range 1.62-2.33, implying that pc lies between 39% and 57%. The errors attached to these estimates of pc suggest that the recommended coverage of 70% would prevent a major outbreak of rabies on no fewer than 96.5% of occasions.
A review of the epidemiology of hepatitis A virus (HAV) infection over the last 20 years shows shifting patterns in the prevalence of antibodies to HAV (anti-HAV) throughout South-East Asia and China. A number of countries have shifted from high to moderate and from moderate to low endemicity, with a corresponding increase in the age of exposure from childhood to early adulthood. The changes have resulted from improvements in hygiene, sanitation and the quality of drinking water, reflecting improvements in living standards and socioeconomic progress. In general in the late 1970s and early 1980s, 85-95% of the population of developing countries like the Philippines, Korea, China and Thailand were anti-HAV-positive by age 10-15 years, compared with only about 50% in the more affluent countries like Malaysia and Singapore. In the early 1990s, 85-95% of the population were immune by age 30-40 years in the Philippines, Korea, China and Thailand, and by 50 years of age and above in Malaysia and Singapore. Similar trends were noted in Hong Kong, Taiwan and Japan. Exposure to HAV at a later age may be associated with an increase in hepatitis A morbidity and a greater propensity for outbreaks.
Asia and Africa have previously been classified as areas of high endemicity for hepatitis B virus (HBV), but in some countries highly effective vaccination programmes have shifted this pattern towards intermediate or low endemicity. Thus, China is now the only country in Asia where HBV endemicity is high. Countries with intermediate endemicity include India, Korea, the Philippines, Taiwan and Thailand, and those with low endemicity include Japan, Pakistan, Bangladesh, Singapore, Sri Lanka and Malaysia. Most countries in Africa have high HBV endemicity, with the exceptions of Tunisia and Morocco, which have intermediate endemicity. Zambia has borderline intermediate/high endemicity. In the Middle East, Bahrain, Iran, Israel and Kuwait are areas of low endemicity, Cyprus, Iraq and the United Arab Emirates have intermediate endemicity, and Egypt, Jordan, Oman, Palestine, Yemen and Saudi Arabia have high endemicity. All of these Middle East countries reach a large proportion of their population with hepatitis B vaccination, which is reducing the infection rate, particularly in Saudi Arabia. The vaccination programme in Taiwan has also greatly reduced the HBV infection rate. Future vaccination programmes must take into account the mode of transmission of HBV, the healthcare infrastructure to deliver vaccination, and the socioeconomic and political factors in each individual country, to determine the most cost-effective way of infection control.
Recombinant Mycobacterium bovis bacille Calmette-Guèrin (rBCG) expressing the malarial epitopes F2R(II)EBA and (NANP)3 as well as two T cell epitopes of the M. tuberculosis ESAT-6 antigen, generated in favour of mycobacterium codon usage elicited specific immune response against these epitopes. Immunised Balb/c mice demonstrated an increase in almost all of the IgG subclasses against both malarial epitopes and enhanced splenocyte proliferative response against the malarial epitopes as well as selected peptides of ESAT-6. Furthermore, flow cytometric analyses showed elevated numbers of CD4+ lymphocytes expressing IFN-gamma and IL-2 against the ESAT-6 peptides, suggesting a specific Th1-mediated response. This study demonstrated that expressing malarial and TB epitopes in a single rBCG construct induced appropriate humoral and cellular immune response against immunogenic epitopes from both organisms.
In this paper, we describe the development of VCUSM2, a live metabolic auxotroph of Vibrio cholerae O139. Auxotrophy was achieved by mutating a house keeping gene, hemA, that encodes for glutamyl-tRNA reductase, an important enzyme in the C5 pathway for delta-aminolevulenic acid (ALA) biosynthesis, which renders this strain dependent on exogenous ALA for survival. Experiments using the infant mouse and adult rabbit models show that VCUSM2 is a good colonizer of the small intestine and elicits greater than a four-fold rise in vibriocidal antibodies in vaccinated rabbits. Rabbits vaccinated with VCUSM2 were fully protected against subsequent challenge with 1 x 10(11) CFU of the virulent wild type (WT) strain. Experiments using ligated ileal loops of rabbits show that VCUSM2 is 2.5-fold less toxic at the dose of 1 x 10(6) CFU compared to the WT strain. Shedding of VCUSM2 in rabbits were found to occur for no longer than 4 days and its maximum survival rate in environmental waters is 8 days compared to the greater than 20 days for the WT strain. VCUSM2 is thus a potential vaccine candidate against infection by V. cholerae O139.
ESWI recommends that the 25 European Union nations strive to vaccinate one-third of their collective population every year by 2010. This translates into an annual vaccine usage of 150 million doses for a population of 455 million. However, the current vaccine usage in Europe is 79 million doses, meaning that only 40% of ESWI's recommended target population is being vaccinated in the EU-25. Indeed, the EU's current risk groups equal about 28% of its population, but it is estimated that less than 62% are being vaccinated with the current vaccine supply--the equivalent of 17% of the total population. Clearly, as ESWI noted in its concluding position paper at the Malta conference, "a large proportion of those traditionally assumed to be at most risk from influenza are not being vaccinated." How to change this and minimize the consequences of a pandemic? "It's very interesting how the arithmetic works, given the goal of immunizing 75 percent of Europe's high-risk group, " said Dr K.Nichol of the University of Minnesota Medical Center who chaired the session. "If you go from a trivalent vaccine to a monovalent one, then you triple the number of doses you can manufacture. Thus, you could produce enough doses for the entire population of the EU." However, there is no coordinated approach in Europe, meaning such an optimistic scenario is unlikely in the medium-term. For the time being, emphasis must be on raising public awareness and raising vaccination rates at the local level, starting with health care workers themselves. Here the role and attitude of health policy officials and--critically--health care workers are crucial. These front-line policy and healthcare professionals constitute both the problem and the solution to a more effective influenza vaccine effort in Europe: they know first-hand the institutional obstacles blocking progress--i.e., lack of resources, poorly focused public information campaigns, etc.--but their own work practices and attitudes can be misdirected, too. To identify the issues and help the participants produce a set of recommendations, ESWI brought in Penny Lawson from to facilitate Dr.K. Nichol to steer this session's workshop debate. The participants were a diverse group of 35 health care workers from Australia, Finland, France, Germany, Malaysia, Malta, Netherlands, Norway, Poland, Portugal, Spain, Sweden and the UK.
Cervical cancer remains one of the leading causes of cancers in women from Indonesia, Malaysia, the Philippines, Thailand and Vietnam. High-risk human papillomavirus (HPV) types, particularly HPV-16 and 18, are consistently identified in cervical cancer cases regardless of geographical region. Factors that have been identified to increase the likelihood of HPV exposure or subsequent development of cervical cancer include young age at first intercourse, high parity and multiple sexual partners. Cervical cancer screening programs in these countries include Pap smears, single visit approach utilizing visual inspection with acetic acid followed by cryotherapy, as well as screening with colposcopy. Uptake of screening remains low in all regions and is further compounded by the lack of basic knowledge women have regarding screening as an opportunity for the prevention of cervical cancer. Prophylactic HPV vaccination with the quadrivalent vaccine has already been approved for use in Malaysia, the Philippines and Thailand, while the bivalent vaccine has also been approved in the Philippines. However, there has been no national or government vaccination policy implemented in any of these countries.
This qualitative study used focus group discussions (FGDs) to evaluate information needed in order to make informed human papillomavirus (HPV) vaccination decision, opinion on the most acceptable public education messages, and channel of delivery in a multiethnic, multicultural and multireligion country. A total of 19 FGDs were conducted among mothers of eligible vaccinees, young women eligible for the vaccine, and men. Messages that carry accurate information about HPV-cervical cancer link, the HPV preventive vaccines and at the same time minimize the stigma of a sexually transmitted infection (STI) vaccine were preferred. Educational messages for future HPV educational intervention were developed and methods to effectively convey to the public the need for HPV vaccination were identified. The findings serve as a basis for future intervention to develop research-based communication materials and strategies.
Physicians' experiences in providing human papillomavirus (HPV) immunization were assessed by mailed questionnaire. Response rate of 41.4% was achieved. Malay Muslim physicians were more likely to agree that cultural sensitivity is an issue when recommending HPV vaccines. Pediatricians and family physicians were more likely to agree that acceptance is better if vaccines were recommended to prevent cervical cancer than to prevent a sexually transmitted disease. Near 70% rated success of HPV vaccines recommendation in their practice as very poor with the majority patients preferred to postpone immunization. Physicians reported cultural disparities in vaccine uptake and perceived high vaccination cost limits its use.
A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel. Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000/microL/day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.
Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination.
This study evaluated whether MF59-adjuvanted subunit trivalent influenza vaccine for the 2003/04 winter season (A/Moscow/10/99, H3N2; A/New Caledonia/20/99, H1N1; B/Hong Kong/330/01) would confer protection against mismatched and frequently co-circulating variants of influenza B/Victoria- and B/Yamagata-like virus strains. Haemagglutination inhibiting (HI) antibodies were measured in middle-aged and elderly volunteers against the homologous B/Victoria-like vaccine strain (B/Hong Kong/330/01) and against mismatched B/Victoria-like (B/Malaysia/2506/04) and B/Yamagata-like (B/Singapore/379/99 and B/Shanghai/361/02) strains. Immunization induced significant increases in the amounts of HI antibodies against all influenza B strains under investigation. However, the responses against the heterologous B/Shanghai/361/02 virus did not reach the desirable values of seroprotection. An age-dependent decline of the responses was found for B/Victoria-like antigens, but not for B/Yamagata-like strains. Although further studies are needed, our data support the recommendation of including influenza B viruses of the B/Victoria and B/Yamagata lineages in the future influenza vaccine preparations.
From August 2006 to July 2007 a prospective study of out-of-pocket costs incurred by care-givers of children hospitalized for rotavirus gastroenteritis was conducted in a hospital in Malaysia. Data on caretaker out-of-pocket costs were collected from 260 children hospitalized with diarrhoea. A stool sample was collected from 198 of these children of which 46 (23%) were positive for rotavirus by latex agglutination assay. The mean (median; interquartile range) out-of-pocket cost incurred by the care-givers was US$194 (US$169; US$47-738), constituting 26% of average monthly income of the households surveyed. Major components of the cost were hospital expenses (45%) and productivity loss (37%). These findings will allow further assessment of the cost-effectiveness of any future rotavirus immunization program in Malaysia.
This paper represents a collaborative effort by the Asian Strategic Alliance for Pneumococcal Disease Prevention (ASAP) Working Group to collate data on the disease burden due to invasive pneumococcal disease (IPD) in participating Asian countries and territories; namely, Hong Kong, India, Indonesia, Korea, Macau, Malaysia, Pakistan, the Philippines, Singapore, Sri Lanka, Taiwan and Thailand. A review of both published and unpublished data revealed that the incidence of IPD in some countries is well documented by way of large, long-duration studies, while in other countries, much of the available data have been extrapolated from international studies or have come from small population studies of limited geographical coverage. This paper confirms that data regarding the incidence of IPD in Asia are grossly lacking and reinforces the need for urgent and more substantial studies.
The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated. Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n=43) or split vaccine (n=47). Two blood samples were collected, one before and one 4-6 weeks after vaccination. Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test. Post-vaccine reactions were recorded over 7 days. Seroconversion rates for H1N1, H3N2 and B were 65.1%, 60.4% and 83.7% for virosome vaccine, and 68.0%, 61.7% and 68.0% for split vaccine. Seroprotection rates for H1N1, H3N2 e B were 100%, 97.6% and 69.7% for virosome, and 97.8%, 97.8% and 76.6% for split vaccine. No severe adverse reactions were recorded. Virosome and split vaccines in patients with sickle cell anemia were equally immunogenic, with high seroconversion and seroprotection rates. Both vaccines were well tolerated.
Burkholderia cepacia is an opportunistic human pathogen associated with lung infections. Secretory proteins of B. cepacia are known to be involved in virulence and may mediate important host-pathogen interactions. In the present study, secretory proteins isolated from B. cepacia culture supernatant were separated using two-dimensional gel electrophoresis, followed by Western blot analysis to identify the immunogenic proteins. Mice antibodies raised to B. cepacia inactivated whole bacteria, outer membrane protein and culture filtrate antigen detected 74, 104 and 32 immunogenic proteins, respectively. Eighteen of these immunogenic proteins which reacted with all three antibodies were identified and might be potential molecules as a diagnostic marker or a putative candidate vaccine against B. cepacia infections.
Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).
To determine why HPV vaccination uptake is low in Asia, we surveyed attitudes, knowledge and communication about cervical cancer and HPV vaccination amongst 480 physicians and 1617 randomly selected urban mothers who could afford HPV vaccines in Korea, Malaysia, Taiwan and Thailand. HPV vaccine rejection by mothers was linked with poor knowledge and low perceptions of self-relevance. Physicians' likelihood of raising the subject and/or recommending vaccination was linked to how proactively they advocate preventive health, their attitude to the subject's sensitivity and their knowledge levels. Because most Asian mothers seek doctors' advice and prefer them to take the initiative, physicians should be more proactive in discussing and recommending HPV vaccination.
Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable.