Abstract

In an era of limited healthcare budgets, mathematical models can be useful tools to identify cost-effective programs and to support policymakers in informed decision making. This paper reports results of our work carried out over several years with the Asian Liver Center at Stanford University, a nonprofit outreach and advocacy organization that is an international leader in the fight against hepatitis B and liver cancer. Hepatitis B is a vaccine-preventable viral disease that, if untreated, can lead to death from cirrhosis and liver cancer. Infection with hepatitis B is a major public health problem, particularly in Asian populations. We used new combinations of decision analysis and Markov models to analyze the cost-effectiveness of several interventions to combat hepatitis B in the United States and China. The results of our OR-based analyses have helped change United States public health policy on hepatitis B screening for millions of people and have helped encourage policymakers in China to enact legislation to provide free catch-up vaccination for hundreds of millions of children. These policies are an important step in eliminating health disparities, reducing discrimination, and ensuring that millions of people who need it can now receive hepatitis B vaccination or lifesaving treatment.

The mechanism by which strictly CCR5 using HIV-1 clade C variants exacerbate disease progression in absence of coreceptor switch is not clearly known. We previously reported HIV-1 cladeC envelopes (Env) obtained from late stage Indian patients with expanded coreceptor tropism. Here we compared such Envs (having expanded coreceptor tropism) with strictly CCR5 using Envs also obtained from late stage in their capacity to utilize CD4 and CCR5 for productive entry. We found that while envelopes with low CD4 dependence tend to infect primary CD4(+) T cells better than those required optimum CD4 for entry, no significant association was found between low CD4 usage and infectivity of primary CD4(+) T cells by Env-pseudotyped viruses and theirsensitivity to CCR5 antagonist TAK-779. Interestingly, Envs that readily infected HeLa cells expressing low CD4 showed relative resistance to T20 indicating that conformational intermediates of these envelopes remained for a shorter period of time than is required for efficient inhibition by T20.

Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped viruses to autologous and heterologous plasma antibodies. When tested against monoclonal antibodies targeting different sites in gp120 and gp41, Envs expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.

Abstract

Although the past few decades have seen rising incomes and increased government attention to rural development, many children in rural China still lack regular access to micronutrient-rich diets. Insufficient diets and poor knowledge of nutrition among the poor result in nutritional problems, including irondeficiency anaemia, which adversely affect attention and learning of students in school. Little research has been conducted in China documenting the prevalence of nutritional problems among vulnerable populations, such as school-age children, in rural areas. The absence of programmes to combat anaemia among students might be interpreted as a sign that the Government does not recognize its severity. The goals of this paper were to measure the prevalence of anaemia among school-age children in poor regions of Qinghai and Ningxia, to identify individual-, household- and school-based factors that correlate with anaemia in this region, and to report on the correlation between the anaemic status and the physical, psychological and cognitive outcomes. The results of a cross-sectional survey are reported here. The survey involved over 4,000 fourth and fifth grade students from 76 randomly-selected elementary schools in 10 poor counties in rural Qinghai province and Ningxia Hui Autonomous Region, located in the northwest region of China. Data were collected using a structured questionnaire and standardized tests. Trained professional nurses administered haemoglobin (Hb) tests (using Hemocue finger prick kits) and measured heights and weights of children. The baseline data showed that the overall anaemia rate was 24.9%, using the World Health Organization's blood Hb cut-offs of 120 g/L for children aged 12 years and older and 115 g/L for children aged 11 years and under. Children who lived and ate at school had higher rates of anaemia, as did children whose parents worked in farms or were away from home. Children with parents who had lower levels of education were more likely to be anaemic. The anaemic status correlated with the adverse physical, cognitive and psychological outcomes among the students. Such findings are consistent with findings of other recent studies in poor, northwest areas of China and led to conclude that anaemia remains a serious health problem among children in parts of China. © International Centre For Diarrhoeal Disease Research, Bangladesh.

In the present study, we investigated genetic divergence between complete autologous HIV-1 env genes amplified directly from plasma of two anti-retroviral naïve, slow progressing Indian patients with broad neutralizing antibody response. All the envelopes (Env) clones obtained from one patient (LT1) belonged to subtype C; the second patient (LT5) harbored quasispecies comprising of pure B, C and B/C recombinants with distinct breakpoints indicative of dual infection with genetically distinct strains. Further characterization of these Envs would provide insights to the biological properties under strong humoral immune response.

Abstract HIV-2 group A is predominant in different parts of the world, especially Africa, Portugal, Spain, France, the United Kingdom, the United States, Korea, and India. Among the Asian countries, India accounts for about 95% of all HIV-2 infections. The prevalence of HIV-2 has been reported from various states of India such as Maharashtra, Goa, Tamil Nadu, West Bengal, and Uttar Pradesh. In the present study, we analyzed transmembrane region (gp36) sequences of 10 HIV-2 group A Indian strains, isolated from Indian HIV-2-seropositive individuals. HIV Blast analysis for the 1.0-Kb region of the gp36 transmembrane region has shown that all these sequences belong to HIV-2 group A. Phylogenetic analysis indicated that the sequences cluster with HIV-2 group A sequences of Cameroon and Senegal. The epitope found at position 645-656 (YELQKLNSWDVF), previously reported as a broadly neutralizing determinant, was very well conserved in all 10 study sequences. The percentage similarity between Indian and South African HIV-2 group A gp36 sequences was 90% (range 86-100, SD 2.8) and with other nonsubtype A clades was 84% (range 77-100, SD 6.06) indicating overall less variability among the reported HIV-2 sequences. Similarly, the consensus amino acid sequences of the envelope transmembrane region of HIV-1 (gp41) and HIV-2 (gp36) is quite synonymous, indicating 87% similarity; however, limited information is available about the gp36 transmembrane region of the prevalent HIV 2 group A Indian strain. The rate of synonymous substitutions reported in the gp105 region was significantly higher, suggesting lower virulence of HIV-2, which does translate into a lower rate of evolution, while the dN/dS ratio for the gp36 transmembrane region was less than one, indicating its conservation and significance (p<0.05) in structural and functional constraints.