Vaccines In Low Income Countries Research Articles

A long-term stable cold-chain-friendly HIV mRNA vaccine encoding multi-epitope viral protease cleavage site immunogens inducing immunogen-specific protective T cell immunity.

The lack of success in clinical trials for HIV vaccines highlights the need to explore novel strategies for vaccine development. Research on highly exposed seronegative (HESN) HIV-resistant Kenyan female sex workers revealed naturally protective immunity is correlated with a focused immune response mediated by virus-specific CD8 T cells. Further studies indicated that the immune response is unconventionally focused on highly conserved sequences around HIV viral protease cleavage sites (VPCS). Thus, taking an unconventional approach to HIV vaccine development, we designed lipid nanoparticles loaded with mRNA that encodes multi-epitopes of VPCS (MEVPCS-mRNA LNP), a strategic design to boost antigen presentation by dendritic cells, promoting effective cellular immunity. Furthermore, we developed a novel cold-chain compatible mRNA LNP formulation, ensuring long-term stability and compatibility with cold-chain storage/transport, widening accessibility of mRNA LNP vaccine in low-income countries. The in-vivo mouse study demonstrated that the vaccinated group generated VPCS-specific CD8 memory T cells, both systemically and at mucosal sites of viral entry. The MEVPCS-mRNA LNP vaccine-induced CD8 T cell immunity closely resembled that of the HESN group and displayed a polyfunctional profile. Notably, it induced minimal to no activation of CD4 T cells. This proof-of-concept study underscores the potential of the MEVPCS-mRNA LNP vaccine in eliciting CD8 T cell memory specific to the highly conserved multiple VPCS, consequently having a broad coverage in human populations and limiting viral escape mutation. The MEVPCS-mRNA LNP vaccine holds promise as a candidate for an effective prophylactic HIV vaccine.

Indirect Effects of the COVID-19 Pandemic on Routine Childhood Vaccination in Low-Income Countries: A Systematic Review to Set the Scope for Future Pandemics.

The COVID-19 pandemic halted progress in global vaccine coverage and disrupted routine childhood vaccination practices worldwide. While there is ample evidence of the vaccination decline experienced during the pandemic, it is less clear how low-income countries were affected. We executed a systematic review to synthesize the current literature on the impacts of routine childhood vaccinations in low-income countries from 1 January 2020 to 8 February 2023. We collected data using an extraction form on Covidence and assessed the quality of studies included in the review using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Effect estimates for changes in vaccination during the pandemic were reported and summarized. Factors that influenced changes were grouped into descriptive themes. Thirteen studies, encompassing 18 low-income countries and evaluating 15 vaccines at varying doses, were included in the final review. We found that routine childhood vaccinations during the COVID-19 pandemic varied considerably by vaccine type, location, and phase of the pandemic. Nine different themes were identified as factors that influenced changes in vaccination. Documenting past experiences and lessons learned is crucial for informing preparedness efforts in anticipation of future public health emergencies. Failure to effectively address these things in the next public health emergency could result in a recurrence of declining routine childhood vaccinations.

Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation

Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child’s vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1–7 days, 8–21 days, and 1–21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19–29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1–7 days: 1.01 (95 %CI: 0.39, 2.60); 8–21 days: 1.37 (95 %CI: 0.81, 2.32); 1–21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1–7 days: 0.81 (95 %CI: 0.42, 1.54); 8–21 days: 0.77 (95 %CI: 0.53, 1.16); 1–21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines.

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors.

Antibiotic use after a typhoid conjugate vaccine: factors beyond vaccination in low-income countries

Antibiotic use after a typhoid conjugate vaccine: factors beyond vaccination in low-income countries

The WTO and the Covid‐19 “Vaccine Apartheid”: Big Pharma and the Minefield of Patents

&lt;p&gt;Unequal access to vaccines for the Covid-19 pandemic, also referred to as “vaccine apartheid,” has marginalized low-income countries again. In October 2020, India and South Africa proposed a temporary waiver from certain provisions of the TRIPS Agreement for the prevention of Covid-19&lt;em&gt; &lt;/em&gt;at the World Trade Organization (WTO). An agreement was later reached in Geneva on June 17, 2022. The objective of this article is to analyze the negotiation and agreement reached at the WTO. This article explores the difficulties of creating international public good in the field of public health within the milieu of powerful actors, namely big pharmaceutical companies with vested interests. The central argument of this article is that this agreement alone will not solve the vaccine access problem for low-income countries. It is too restrictive, does not cover trade secrets and know-how, production capacity, availability of raw materials, and even adds new limitations that did not exist before. The best option to promote the production of quality vaccines in low-income countries is to share technology and know-how on a voluntary basis through production agreements. One way to facilitate the cooperation of large pharmaceutical corporation is to make it easier for low-income countries to use compulsory licenses. Simplifying the use of this mechanism could help encourage pharmaceutical companies to enter into voluntary licensing agreements.&lt;/p&gt;

MRNA vaccines: The future of prevention of viral infections?

Messenger RNA (mRNA) vaccines against COVID-19 are the first authorized biological preparations developed using this platform. During the pandemic, their administration has been proven to be a life-saving intervention. Here, we review the main advantages of using mRNA vaccines, identify further technological challenges to be met during the development of the mRNA platform, and provide an update on the clinical progress on leading mRNA vaccine candidates against different viruses that include influenza viruses, human immunodeficiency virus 1, respiratory syncytial virus, Nipah virus, Zika virus, human cytomegalovirus, and Epstein-Barr virus. The prospects and challenges of manufacturing mRNA vaccines in low-income countries are also discussed. The ongoing interest and research in mRNA technology are likely to overcome some existing challenges for this technology (e.g., related to storage conditions and immunogenicity of some components of lipid nanoparticles) and enhance the portfolio of vaccines against diseases for which classical formulations are already authorized. It may also open novel pathways of protection against infections and their consequences for which no safe and efficient immunization methods are currently available.

Current Update on Rotavirus in-Silico Multiepitope Vaccine Design.

Rotavirus gastroenteritis is one of the leading causes of pediatric morbidity and mortality worldwide in infants and under-five populations. The World Health Organization (WHO) recommended global incorporation of the rotavirus vaccine in national immunization programs to alleviate the burden of the disease. Implementation of the rotavirus vaccination in certain regions of the world brought about a significant and consistent reduction of rotavirus-associated hospitalizations. However, the efficacy of licensed vaccines remains suboptimal in low-income countries where the incidences of rotavirus gastroenteritis continue to happen unabated. The problem of low efficacy of currently licensed oral rotavirus vaccines in low-income countries necessitates continuous exploration, design, and development of new rotavirus vaccines. Traditional vaccine development is a complex, expensive, labor-intensive, and time-consuming process. Reverse vaccinology essentially utilizes the genome and proteome information on pathogens and has opened new avenues for in-silico multiepitope vaccine design for a plethora of pathogens, promising time reduction in the complete vaccine development pipeline by complementing the traditional vaccinology approach. A substantial number of reviews on licensed rotavirus vaccines and those under evaluation are already available in the literature. However, a collective account of rotavirus in-silico vaccines is lacking in the literature, and such an account may further fuel the interest of researchers to use reverse vaccinology to expedite the vaccine development process. Therefore, the main focus of this review is to summarize the research endeavors undertaken for the design and development of rotavirus vaccines by the reverse vaccinology approach utilizing the tools of immunoinformatics.

Global impact of the first year of COVID-19 vaccination: a mathematical modelling study

BackgroundThe first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021. We aimed to quantify the global impact of the first year of COVID-19 vaccination programmes.MethodsA mathematical model of COVID-19 transmission and vaccination was separately fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. The impact of COVID-19 vaccination programmes was determined by estimating the additional lives lost if no vaccines had been distributed. We also estimated the additional deaths that would have been averted had the vaccination coverage targets of 20% set by COVAX and 40% set by WHO been achieved by the end of 2021.FindingsBased on official reported COVID-19 deaths, we estimated that vaccinations prevented 14·4 million (95% credible interval [Crl] 13·7–15·9) deaths from COVID-19 in 185 countries and territories between Dec 8, 2020, and Dec 8, 2021. This estimate rose to 19·8 million (95% Crl 19·1–20·4) deaths from COVID-19 averted when we used excess deaths as an estimate of the true extent of the pandemic, representing a global reduction of 63% in total deaths (19·8 million of 31·4 million) during the first year of COVID-19 vaccination. In COVAX Advance Market Commitment countries, we estimated that 41% of excess mortality (7·4 million [95% Crl 6·8–7·7] of 17·9 million deaths) was averted. In low-income countries, we estimated that an additional 45% (95% CrI 42–49) of deaths could have been averted had the 20% vaccination coverage target set by COVAX been met by each country, and that an additional 111% (105–118) of deaths could have been averted had the 40% target set by WHO been met by each country by the end of 2021.InterpretationCOVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage.FundingSchmidt Science Fellowship in partnership with the Rhodes Trust; WHO; UK Medical Research Council; Gavi, the Vaccine Alliance; Bill & Melinda Gates Foundation; National Institute for Health Research; and Community Jameel.

Assessing Vaccination Prioritization Strategies for COVID-19 in South Africa Based on Age-Specific Compartment Model

The vaccines are considered to be important for the prevention and control of coronavirus disease 2019 (COVID-19). However, considering the limited vaccine supply within an extended period of time in many countries where COVID-19 vaccine booster shot are taken and new vaccines are developed to suppress the mutation of virus, designing an effective vaccination strategy is extremely important to reduce the number of deaths and infections. Then, the simulations were implemented to study the relative reduction in morbidity and mortality of vaccine allocation strategies by using the proposed model and actual South Africa's epidemiological data. Our results indicated that in light of South Africa's demographics, vaccinating older age groups (>60 years) largely reduced the cumulative deaths and the “0–20 first” strategy was the most effective way to reduce confirmed cases. In addition, “21–30 first” and “31–40 first” strategies have also had a positive effect. Partial vaccination resulted in lower numbers of infections and deaths under different control measures compared with full vaccination in low-income countries. In addition, we analyzed the sensitivity of daily testing volume and infection rate, which are critical to optimize vaccine allocation. However, comprehensive reduction in infections was mainly affected by the vaccine proportion of the target age group. An increase in the proportion of vaccines given priority to “0–20” groups always had a favorable effect, and the prioritizing vaccine allocation among the “60+” age group with 60% of the total amount of vaccine consistently resulted in the greatest reduction in deaths. Meanwhile, we observed a significant distinction in the effect of COVID-19 vaccine allocation policies under varying priority strategies on relative reductions in the effective reproduction number. Our results could help evaluate to control measures performance and the improvement of vaccine allocation strategy for COVID-19 epidemic.

Willingness to take COVID-19 vaccination in low-income countries: Evidence from Ethiopia.

BackgroundIn low-income countries, vaccination campaigns are lagging, and evidence on vaccine acceptance, a crucial public health planning input, remains scant. This is the first study that reports willingness to take COVID-19 vaccines and its socio-demographic correlates in Ethiopia, Africa’s second most populous country.MethodsThe analysis is based on a nationally representative survey data of 2,317 households conducted in the informal economy in November 2020. It employs two logistic regression models where the two outcome variables are (i) a household head’s willingness to take a COVID-19 vaccine or not, and (ii) if yes if they would also hypothetically pay (an unspecified amount) for it or not. Predictors include age, gender, education, marital status, income category, health insurance coverage, sickness due to COVID-19, chronic illness, trust in government, prior participation in voluntary activities, urban residence.ResultsWillingness to take the vaccine was high (88%) and significantly associated with COVID-19 cases in the family, trust in government and pro-social behavior. All other predictors such as gender, education, income, health insurance, chronic illness, urban residence did not significantly predict vaccine willingness at the 5% level. Among those willing to take the vaccine, 33% also answered that they would hypothetically pay (an unspecified amount) for it, an answer that is significantly associated with trust in government, health insurance coverage and income.ConclusionThe results highlight both opportunities and challenges. There is little evidence of vaccine hesitancy in Ethiopia among household heads operating in the informal economy. The role played by trust in government and pro-social behavior in motivating this outcome suggests that policy makers need to consider these factors in the planning of COVID-19 vaccine campaigns in order to foster vaccine uptake. At the same time, as the willingness to hypothetically pay for a COVID-19 vaccine seems to be small, fairly-priced vaccines along with financial support are also needed to ensure further uptake of COVID-19 vaccines.

Patients' Acceptance of COVID-19 Vaccine: Implications for Patients with Chronic Disease in Low-Resource Settings.

Coronavirus disease 2019 (COVID-19) has become a major global health challenge, with high morbidity and mortality. Despite different vaccines being produced around the globe, the spread of the virus is still uncontrolled. In particular, the shortage of vaccines in low-income countries is one of the key factors hindering efforts to reduce the spread of the virus. Even though evidence has been provided by different responsible bodies, there are still multiple beliefs and misconceptions about COVID-19 vaccination that have not yet been addressed. Nowadays, vaccine hesitancy is one of the top ten threats to global health, arising from the unwillingness of chronic patients to receive the vaccine. Chronic disease patients in low-resource settings are fearful of taking the vaccine because of a shortage of information about the COVID-19 vaccine. Therefore, the acceptance of the COVID-19 vaccine among chronic disease patients should be studied more widely in low-resource settings.

Next-generation rotavirus vaccines: important progress but work still to be done

Rotavirus vaccines reduce the number of hospital admissions for diarrhoea caused by rotavirus in children younger than 5 years and are cost-effective when implemented within national immunisation programmes.1,2 Yet only 35% of eligible infants worldwide receive rotavirus vaccination, leaving 89 million children unprotected.3 Although funding from Gavi, the Vaccine Alliance, has facilitated the introduction of rotavirus vaccines in low-income countries, countries with transitioning economies and middle-income countries have struggled to prioritise rotavirus vaccines for inclusion in infant vaccination programmes because of demand for other vaccines and increasing health-care costs.

Prevalence and Factors Associated with Rotavirus Infection among Vaccinated Children Hospitalized for Acute Diarrhea in Mwanza City, Tanzania: A Cross Sectional Study

Introduction: Rotavirus infection is a leading cause of severe diarrhea culminating to dehydration among children under five years of age. Understanding trends and factors that could assist towards devising effective preventive strategies of Rotavirus infection beyond vaccination is crucial. Objectives: This study was done in an attempt to determine the prevalence and associated factors of Rotavirus infection among vaccinated children aged between 6 weeks and 24 months admitted with acute diarrhea Mwanza, Tanzania. Material and Methods: Across sectional study involving vaccinated children aged 6 weeks to 24 months was conducted in three selected hospitals from July 2017 to January 2018. Socio-demographic and other relevant clinical information were collected using a standardized data collection tool adopted from WHO Rotavirus surveillance tool. Rotavirus infection from the stool was detected using an enzyme immunoassay. Data were analyzed using STATA version 13. Results: A total of 301 vaccinated children with acute diarrhea with a median age of 12 [IQR: 8 - 17] months were enrolled. Nine (3.0%) and 292 (97.0%) had received one dose and two doses of Rotavirus vaccine, respectively. The prevalence of Rotavirus infection was 74 (24.6%) [95% CI: 20.0 - 29.8]. Independent predictors of Rotavirus infection were: dry season (OR 6.9; 95% CI: 2.9 - 16.0; p - 4.2; p = 0.043) and vomiting (OR 3.6; 95% CI 1.1 - 12.6; p = 0.045). Children with Rotavirus infection had a significantly shorter hospital stay than those without Rotavirus infection (3 [2 - 4] days versus 3 [3 - 5] days; p = 0.0297). Conclusions: The prevalence of Rotavirus infection has declined among vaccinated children in Mwanza, Tanzania with significant decrease in the hospital stay. Dry seasons, three or more children indwelling in the same house and vomiting were independent predictors of Rotavirus infection. There is a need to sustain the coverage of rotavirus vaccination in low-income countries in order to significantly reduce associated morbidity and mortality.

Evolution of P[8], P[4], and P[6] VP8* genes of human rotaviruses globally reported during 1974 and 2017: possible implications for rotavirus vaccines in development

ABSTRACT Non-replicating parenteral rotavirus (RV) vaccine candidates are in development in an attempt to overcome the lower efficacy and effectiveness of oral RV vaccines in low-income countries. One of the leading candidates is a truncated recombinant VP8* protein, expressed in Escherichia coli from original sequences of the prototype RV genotypes P[8], P[4], or P[6] isolated before 1983. Since VP8* is highly variable, it was considered useful to examine the evolutionary changes of RV strains reported worldwide over time in relation to the three P2-VP8 vaccine strains. Here, we retrieved from the GenBank 6,366 RV VP8* gene sequences of P[8], P[4], or P[6] strains isolated between 1974 and 2017, in 77 countries, and compared them with those of the three P2-VP8 vaccine strains: Wa (USA, 1974, G1P[8]), DS-1 (USA, 1976, G2P[4]), and 1076 (Sweden, 1983, G2P[6]). Phylogenetic analysis showed that 94.9% (4,328/4,560), 99.8% (1,141/1,143), and 100% (663/663) of the P[8], P[4], and P[6] strains, respectively, reported globally between 1974 and 2018 belong to non-vaccine lineages. These P[8], P[4], and P[6] RV strains have a mean of 9%, 5%, and 6% amino acid difference from the corresponding vaccine strains. Additionally, in the USA, the mean percentage difference between all the P[8] RV strains and the original Wa strain increased over time: 4% (during 1974–1980), 5% (1988–1991), and 9% (2005–2013). Our analysis substantiated high evolutionary changes in VP8* of the P[8], P[4], and P[6] major RV strains and their increasing variations from the candidate subunit vaccine strains over time. These findings may have implications for the development of new RV vaccines.

Systematic Review and Meta-Analysis of Cost-effectiveness of Rotavirus Vaccine in Low-Income and Lower-Middle-Income Countries.

BackgroundRotavirus causes morbidity and mortality in children particularly in low-income countries (LICs) and lower-middle-income countries (LMICs). This systematic review and meta-analysis aimed to assess cost-effectiveness of rotavirus vaccine in LICs and LMICs.MethodsRelevant studies were identified from PubMed and Scopus from their inception to January 2019. Studies were eligible if they assessed the cost-effectiveness of rotavirus vaccine in children in LICs and LMICs and reported incremental cost-effectiveness ratios. Risk of bias and quality assessment was assessed based on the Consolidated Health Economic Evaluation Reporting Standard checklist. Incremental net benefits (INBs) were estimated, and meta-analysis based on the DerSimonian and Laird method was applied to pool INBs across studies.ResultsWe identified 1614 studies, of which 28 studies (29 countries) were eligible and conducted using cost-utility analysis in LICs (n = 8) and LMICs (n = 21). The pooled INB was estimated at $62.17 (95% confidence interval, $7.12–$117.21) in LICs, with a highly significant heterogeneity (χ2 = 33.96; df = 6; P < .001; I2 = 82.3%), whereas the pooled INB in LMICs was $82.46 (95% confidence interval, $54.52–$110.41) with no heterogeneity (χ2 = 8.46; df = 11; P = .67; I2 = 0%).ConclusionsRotavirus vaccine would be cost-effective to introduce in LICs and LMICs. These findings could aid decision makers and provide evidence for introduction of rotavirus vaccination.

Observational studies of non-specific effects of Diphtheria-Tetanus-Pertussis vaccines in low-income countries: Assessing the potential impact of study characteristics, bias and confounding through meta-regression

IntroductionIt has been suggested that some vaccines have effects beyond protection against the diseases they target, called non-specific effects (NSEs). In 2016, a systematic review by Higgins et al., commissioned by the WHO Strategic Advisory Group of Experts (SAGE) on immunization, estimated the relative risk (RR) of all-cause mortality after whole-cell Diphtheria-Tetanus-Pertussis (DTwP) vaccination to be 1.38 (95% CI: 0.92–2.08), and described these potential NSEs as inconsistent. However, the selection of studies for meta-analysis, based on their proneness to bias and confounding, was debated. ObjectiveTo identify study characteristics and postulated risks of bias and confounding that might have impacted the RR of all-cause mortality after DTwP vaccination in observational studies conducted in low-income countries. MethodsBased on methodological considerations on study design and analysis, we systematically assessed all 17 DTwP studies from the Higgins et al. review for risk of selection bias, exposure and outcome misclassification, confounding and differential co-interventions. We used meta-regression to assess the impact of study characteristics and the postulated risks of bias and confounding on the RR estimates, and looked for outlying and influential risk estimates. Permutation tests were performed to control for false-positive findings. ResultsThe overall RR of all-cause mortality after DTwP vaccination including all but one outlying and influential study was 1.32 (95% CI: 0.83–2.08). Based on uni-variable meta-regression, we found that study location (p = 0.01), studies using the landmark approach (p = 0.015) and studies at high risk of exposure misclassification (p = 0.036) were significantly associated with increased RR estimates whereas studies at high risk of selection bias (p = 0.059) showed borderline significance. The results further suggest these effect modifiers are clustered in studies conducted in West-Africa. ConclusionThe increased RR of all-cause mortality after DTwP might be confined to West-African countries and/or certain postulated risks of bias might have inflated these RRs.

A review on thimerosal: an irreplaceable element of long-term immunisation strategy in low income countries

Thimerosal, an organic-mercury (Hg) compound containing 49.55% Hg by weight, is added to vaccines as a preservative permitting formulation of multi-dose vaccine vials. Being a derivative of ethylmercury, it has been linked with autism as a possible risk factor based on the assumption that exposure to ethylmercury would have similar neurotoxic effects as another mercurial compound, methylmercury. In 1999, AAP issued a joint statement emphasising the removal of thimerosal from vaccines. Subsequently, several studies have been conducted; those showing positive association between thimerosal exposure and autism have been recognised to be fraught with methodological flaws. On the other hand, many well controlled studies have failed to find any such causal relation and there are others that have clearly demonstrated a much favourable kinetic profile of ethylmercury as compared to methylmercury. Owing to the lack of data, AAP retired its original statement in 2002. Recently, thimerosal has been exempted from regulation by Minamata Convention on Mercury resulting in the continued use of low cost thimerosal containing vaccines in low income countries which cannot afford to run their immunisation program using single dose thimerosal free vaccines, that comparatively cost much higher, as is the case in high income countries. Some bodies view this as a discrimination on the basis of wealth of a nation and have opposed this decision. This review presents various studies regarding the causal association between thimerosal containing vaccines and autism. The current evidence fails to support any such association. Hence this review supports the exemption of thimerosal from regulation and also justifies its use in LICs for uninterrupted vaccination of the most vulnerable population.

Measuring indirect effects of rotavirus vaccine in low income countries

Widespread introduction of rotavirus vaccines has led to major reductions in the burden of rotavirus gastroenteritis worldwide. Vaccine effectiveness is diminished, however, in low income countries, that harbour the greatest burden of rotavirus attributed morbidity and mortality. Indirect effects of rotavirus vaccine (herd immunity and herd protection) could increase population level impact and improve vaccine cost effectiveness in such settings. While rotavirus vaccine indirect effects have been demonstrated in high and middle income countries, there are very little data from low income countries where force of infection, population structures and vaccine schedules differ. Targeted efforts to evaluate indirect effects of rotavirus vaccine in low income countries are required to understand the total impact of rotavirus vaccine on the global burden of rotavirus disease.

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.