Vaccines In Low Income Countries Research Articles

Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli.

Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology.

Qualitative study of the feasibility of HPV vaccine delivery to young adolescent girls in Vietnam: evidence from a government-implemented demonstration program.

BackgroundIntroduction of human papillomavirus (HPV) vaccine in national programs has proceeded apace since 2006, mostly in high-income countries. Recently concluded pilots of HPV vaccination in low-income countries have provided important lessons learned for these settings; however, rigorous evaluations of the feasibility of these delivery strategies that effectively reach young adolescents have been few. This paper presents results from a qualitative evaluation of a demonstration program which implemented school-based and health center–based HPV vaccinations to all girls in grade 6, or 11 years of age, for two years in four districts of Vietnam.MethodsUsing semi-structured interviews of 131 health and education staff from local, district, province, and national levels and 26 focus-group discussions with local project implementers (n = 153), we conducted a qualitative two-year evaluation to measure the impact of HPV vaccinations on the health and education systems.ResultsHPV vaccine delivery at schools or health centers was made feasible by: a. close collaboration between the health and education sectors, b. detailed planning for implementation, c. clearly defined roles and responsibilities for project implementers, d. effective management and supervision of vaccinations during delivery, and e. engagement with community organizations for support. Both the health and education systems were temporarily challenged with the extra workload, but the disruptions were short-lived (a few days for each of three doses) and perceived as worth the longer-term benefit of cervical cancer prevention.ConclusionThe learning from Vietnam has identified critical elements for successful vaccine delivery that can provide a model for other countries to consider during their planning of national rollout of HPV vaccine.

Improving access to vaccines through tiered pricing

Improving access to vaccines through tiered pricing

Update on bacterial meningitis

Bacterial meningitis is a life-threatening disease that continues to inflict a heavy toll. We reviewed recent advances in vaccination, randomized studies on treatment, and genetic association studies in bacterial meningitis. The incidence of bacterial meningitis has decreased after implementation of vaccines, and further implementation of existing conjugate vaccines particularly in low-income countries is expected to reduce the global disease burden. Several randomized studies have been performed recently in this field. Clinical studies showed that short duration (5 days) of antibiotic treatment is as effective as longer duration treatment in low-income countries, and that dexamethasone decreases death and neurological sequelae in high-income countries. Ongoing trials will further define the role of paracetamol, glycerol and hypothermia in bacterial meningitis. Genetic association studies identified pathophysiological mechanisms that could be counteracted in experimental meningitis, providing promising leads for future treatments. Conjugate vaccines have reduced the burden of bacterial meningitis in high-income countries, but implementation of available vaccines in low-income countries is necessary to reduce disease burden worldwide. Adjunctive dexamethasone therapy has beneficial effects in patients with bacterial meningitis but only in high-income countries. Genetic association studies may reveal targets for new treatment strategies.

GAVI to fund HPV vaccines in low-income countries

Eight low-income countries are to receive support from the Global Alliance for Vaccines and Immunisation (GAVI) for pilot HPV vaccination schemes. GAVI made the announcement to coincide with World Cancer Day on Feb 4, 2013. Ghana, Kenya, Laos, Madagascar, Malawi, Niger, Sierra Leone, and Tanzania will vaccinate girls aged 9–13 years in school-based and community-based programmes.

Reduced price on rotavirus vaccines: enough to facilitate access where most needed?

Rotavirus infections, the most common cause of severe childhood diarrhoea, result in approximately 527 000 child deaths every year. The majority of these deaths occur in low-income countries, particularly in Africa and Asia.1 Rotavirus-associated diarrhoea can be prevented by new live attenuated human rotavirus vaccines. These vaccines have proved safe and efficacious in large-scale clinical trials and post-licensure studies have confirmed their effectiveness in middle- and high-income countries.2,3 However, they have only been partially implemented in national immunization programmes in low-income countries, even though these countries have higher rates of death from rotavirus infection.4 The pharmaceutical companies behind the two internationally licensed rotavirus vaccines, Rotarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium) and RotaTeq® (Merck & Co. Inc., Whitehouse Station, United States of America), have recently pledged to the United Nations Children’s Fund and the international donor community to provide their vaccines to low-income countries at greatly reduced prices.4,5 In spite of these reductions, rotavirus vaccines continue to be more expensive than most traditional childhood vaccines included in the Expanded Programme on Immunization (EPI). This rekindles the traditional debate surrounding access to new childhood vaccines in low-income countries. In this paper, we examine whether the newly-proposed vaccine prices are low enough to make rotavirus vaccines universally accessible to the millions of children in need of protection against rotavirus infection, a major threat to child health. Furthermore, we discuss the steps that need to be taken in the future to facilitate the introduction of rotavirus vaccines and ensure their sustained financing in low-income countries.

Multiple virus infection alters rotavirus replication and expression of cytokines and Toll-like receptors in intestinal epithelial cells

Two live oral rotavirus vaccines have shown to be effective in protecting young children from severe illness in developed and middle income countries, but their efficacy is significantly lower in low income countries. One of the reasons for this lower efficacy may be mixed virus infection in the gut that is commonly encountered among infants in the developing world. We investigated whether multiple virus infection interferes with rotavirus replication and alters host response by comparing single and mixed enteric virus infections in Caco-2 cells. We observed a dramatic reduction in rotavirus replication and growth in mixed rotavirus, astrovirus and enterovirus infection compared to single rotavirus infection. By contrast, the levels of astrovirus and enterovirus RNA in mixed infection remained unchanged when compared to those of the corresponding single virus infection. We then examined cells with single or multiple virus infections for the expression of 10 cytokine genes and demonstrated elevated expressions for 7 (IFN-α, IFN-β, IFN-γ, TNF-α, IL-6, IL-8, and IL-17) in dual rotavirus and enterovirus or triple rotavirus, enterovirus and astrovirus-infected cells but only 3 (IFN-β, TNF-α, and IL-8) in dual rotavirus and astrovirus-infected cells. We further observed elevated levels of TLR4, TLR5, TLR7 and TLR9 mRNAs in cells with rotavirus and enterovirus or rotavirus, enterovirus and astrovirus infections when compared to single rotavirus infections. Our data suggest that rotavirus infection is susceptible to interference by other enteric viruses in the gut, which could result in reduced virus replication and contribute to lower immunogenicity and efficacy of oral rotavirus vaccines in low income countries.

Interactions of diarrhea, pneumonia, and malnutrition in childhood: recent evidence from developing countries.

This review highlights recent progress toward understanding complex interactions between diarrhea, pneumonia, and undernutrition among children in low-income and middle-income countries. New studies parallel earlier reports that diarrhea and pneumonia impair children's growth and that underlying malnutrition is a major risk factor for these conditions. Episodes of diarrhea may predispose to pneumonia in undernourished children. Additional studies support breastfeeding and micronutrient supplementation for the prevention and control of diarrhea and pneumonia. Malnutrition may partially account for the reduced efficacy of oral rotavirus vaccines in low-income countries. Immunization of pregnant women against influenza also appears to reduce intrauterine growth retardation. Immunization of infants against Streptococcus pneumoniae may improve their growth. New genetic studies indicate that polymorphisms in apolipoprotein E or the leptin receptor modulate children's risk for diarrhea and Entamoeba histolytica infection, respectively, thereby linking two genes important for lipid metabolism to enteric infections. Significant advances have been made in understanding the vicious cycle of malnutrition, diarrhea, and pneumonia in developing countries. Future challenges will be to translate this progress into effective and widely accessible public health measures.

Evaluation of cost-effective strategies for rabies post-exposure vaccination in low-income countries.

BackgroundPrompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized.Methodology/Principal FindingsWe analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than $60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs.Conclusions/SignificanceWe conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers.

Overcoming Barriers and Ensuring Access to HPV Vaccines in Low-Income Countries

The inequitable burden of cervical cancer falls on women in poorer countries, due primarily to a disparity in access to screening services. To ensure that access to the new human papillomavirus ("HPV") vaccines is not similarly skewed toward higher-income populations, it is important to understand the appropriate priority group for receiving vaccines, the potential barriers to reaching that group, and the options for overcoming those barriers. Based on vaccine efficacy data, the likelihood of achieving high coverage with various groups, and the resultant cost-effectiveness ratios, it is widely agreed that young adolescent girls should be the primary recipients. Potential barriers include the fact that young adolescents are not currently reached by many health services; that there might be stigma attached to a vaccine for a sexually transmitted infection; that financing for the vaccine must be allocated; and that there is limited political commitment to women's health, to cancer prevention, or to this particular vaccine when so many other new vaccines are also becoming available. Despite these very real challenges, there is reason to be cautiously optimistic that those most in need of an HPV vaccine can receive it in programs that are affordable, effective, and acceptable to girls, their families, and their societies.

Scheduling of measles vaccination in low-income countries: Projections of a dynamic model

Large-scale vaccination campaigns (SIAs) and improved routine immunization (RI) have greatly reduced measles incidence in low-income countries. However, the interval between SIAs required to maintain these gains over the long term is not clear. We developed a dynamic model of measles transmission to assess measles vaccination strategies in Cambodia, Ghana, India, Morocco, Nigeria, and Uganda. We projected measles cases from 2008 to 2050 under (a) holding SIAs every 2, 4, 6, or 8 years, (b) improvements in first dose routine measles vaccine (MCV1) coverage of 0%, 1%, 3% annually, and (c) introducing MCV2 once MCV1 coverage reaches 70%, 80%, 90%. If MCV1 continues improving, then India and Nigeria could hold SIAs every 4 years without significant probability of large outbreaks, and the other countries every 6–8 years. If RI remains stagnant, India and Nigeria should hold SIAs every 2 years, and the other countries every 4–6 years.

Economic evaluation of hepatitis B vaccination in low-income countries: using cost-effectiveness affordability curves

We sought to describe a method that explicitly considers both a health-care programmes cost-effectiveness and its affordability. For illustration, we apply the method to the programme to vaccinate infants against hepatitis B in the Gambia. We synthesized selected data and developed a computer-based model from the societal and payer perspectives to evaluate the cost-effectiveness of routine infant vaccination against hepatitis B in the Gambia compared with no vaccination. The primary outcome measure was cost per averted disability-adjusted life year (DALY), which was expressed in 2002 US dollars. We used Monte Carlo methods for uncertainty analysis to examine the affordability of the programme from the payers perspective, and we derived an affordability curve and cost-effectiveness affordability curves for the programme. In the Gambia, vaccinating infants against hepatitis B is highly cost-effective. Compared with offering no intervention, the vaccination programme would cost US$ 28 per DALY averted from the societal perspective or US$ 47 per DALY averted from the payers perspective. The programme also has the potential to be affordable, starting at a relatively low budget of US$ 160,000 per year. Combining the two dimensions of the outcome measure, the probability that vaccinating infants would be both cost-effective and affordable is 40% at an annual programme budget of US$ 182,000 (the estimated total programme cost from the payers perspective), given a threshold cost-effectiveness value of US$ 47 per DALY averted. In the face of uncertainties about both the health and economic consequences of a vaccine programme, as well as the availability and magnitude of resources needed to fund the programme, cost-effectiveness affordability curves can provide information to decision-makers about the probability that a programme will be both cost-effective and affordable: these are distinct but equally relevant considerations in resource-poor settings.

Reproductive Health and New Technologies in Africa: Horizon Scanning for New Technologies

Reproductive health and new technologies in Africa: the horizon in search of new programs Men and women in developing countries must take advantage of recent advances in the development of sexual health technologies. Chlamydia screening, HPV screening and vaccination, vaccine testing of HSV-1 and the new diagnostic test for sexually transmitted infections (STIs) have the potential to reduce the burden of sexually transmitted infections. Screening for chlamydia has been done in several European countries, but it is too expensive for developing countries where the problem is the prevalence of chlamydia and its complications are much more enormous. Ethical issues regarding the implementation of HPV vaccination are discussed as vaccine becomes available in rich countries. The cost of HIV testing was once very expensive for many developing countries, but the importance of this intervention in relation to the treatment of the HIV pandemic has led to improvements in the quality of screening and reductions Dramatic costs. We must learn the lessons of the HIV epidemic for the introduction of new technologies in poor resource conditions in the future. In particular, it is necessary to assess and consider the social context of the communities that should benefit from it. The development and very rapid manner of which one of two vaccines which have demonstrated, during the tests, their high efficiency in the prevention of infection in women who are infected by the major types of the human papillomavirus (HPV) has Initiated discussions on the possibility of efficacy of this vaccine in low-income countries. Consideration must be given to cost, delivery, access and acceptability of access, if new technology is introduced, but a partial or incomplete understanding of the social and cultural context aggravates the difficulties. Keywords: reproductive health, sexually transmitted infections, HPV, acceptability, Kenya Keywords: Reproductive health, sexually tranmitted infections, HPV, acceptability, Kenya

Transients and attractors in epidemics.

Historical records of childhood disease incidence reveal complex dynamics. For measles, a simple model has indicated that epidemic patterns represent attractors of a nonlinear dynamic system and that transitions between different attractors are driven by slow changes in birth rates and vaccination levels. The same analysis can explain the main features of chickenpox dynamics, but fails for rubella and whooping cough. We show that an additional (perturbative) analysis of the model, together with knowledge of the population size in question, can account for all the observed incidence patterns by predicting how stochastically sustained transient dynamics should be manifested in these systems.