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HIV type 1 mutational patterns in HIV type 1 subtype C-infected long-term survivors in Karonga District Malawi: further analysis and correction.

ABSTRACT: Here we present new sequence data from HIV-1 subtype C-infected long-term survivors (LTS) from Karonga District, Malawi. Gag and env sequence data were produced from nine individuals each of whom has been HIV-1 positive for more than 20 years. We show that the three amino acid deletion in gag p17 previously described from these LTS is not real and was a result of an alignment error. We find that the use of dried blood spots for DNA-based studies is limited after storage for 20 years. We also show some unlikely amino acid changes in env C2-V3 in LTS over time and different patterns of genetic divergence among LTS. Although no clear association between mutations and survival could be shown, amino acid changes that are present in more than one LTS may, in the future, be shown to be important.

SUBMITTER: Seager I

PROVIDER: S-EPMC3292752 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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HIV type 1 mutational patterns in HIV type 1 subtype C-infected long-term survivors in Karonga District Malawi: further analysis and correction.

Seager Ishla I Leeson Michael D MD Crampin Amelia C AC Mulawa Dominic D French Neil N Glynn Judith R JR Travers Simon A A SA McCormack Grace P GP

AIDS research and human retroviruses 20110830 3

Here we present new sequence data from HIV-1 subtype C-infected long-term survivors (LTS) from Karonga District, Malawi. Gag and env sequence data were produced from nine individuals each of whom has been HIV-1 positive for more than 20 years. We show that the three amino acid deletion in gag p17 previously described from these LTS is not real and was a result of an alignment error. We find that the use of dried blood spots for DNA-based studies is limited after storage for 20 years. We also sho ...[more]

PMID: 21702696

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Project description:IntroductionStunting or linear growth retardation in childhood is associated with delayed cognitive development due to related causes (malnutrition, illness, poor stimulation), which leads to poor school outcomes at later ages, although evidence of the association between the timing and persistence of stunting and school outcomes within the sub-Saharan African context is limited.MethodsAnthropometric data around birth (0-4 months), early (11-16 months) and late childhood (ages 4-8 years) along with school outcomes up until the age of 11 were analysed for a cohort of 1,044 respondents, born between 2002-2004 in Karonga district, northern Malawi. The schooling outcomes were age at school enrolment, grade repetition in Standard 1 and age-for-grade by age 11. Height-for-Age Z-scores (HAZ) and growth trajectories were examined as predictors, based on stunting (<-2SD HAZ) and on trajectories between early and late childhood (never stunted, improvers, decliners or persistently stunted). Multinomial and logistic regression were used to estimate the association between stunting/trajectories and schooling, adjusted for socioeconomic confounders.ResultsThe effects of stunting on schooling were evident in early childhood but were more pronounced in late childhood. Children who were stunted in early childhood (9.3%) were less likely to be underage at enrolment, more likely to repeat Standard 1 and were 2-3 times more likely to be overage for their grade by the age of 11, compared to their non-stunted peers. Those persistently stunted between early and late childhood (7.3%) faced the worst consequences on schooling, being three times as likely to enrol late and 3-5 times more likely to be overage for their grade by the age of 11, compared to those never stunted. Compared to improvers, those persistently stunted were three times as likely to be overage by two or more years by the age of 11, with no effect on enrolment or repetition.ConclusionOur findings confirm the importance of early childhood stunting on schooling outcomes and suggest some mitigation by improvements in growth by the age of starting school. The nutritional and learning needs of those persistently stunted may need to be prioritised in future interventions.

Project description:BackgroundThirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced in Malawi in November 2011 and is offered to infants at 6, 10 and 14?weeks of age as part of routine immunisation. PCV13 is expected to reduce vaccine type (VT) nasopharyngeal carriage, leading to reduced transmission and herd protection.MethodsWe compared pneumococcal carriage in rural Karonga District, Malawi, pre-vaccine in 2009-2011 and post-vaccine in 2014 using a combination of cross-sectional and longitudinal analyses. Nasopharyngeal swabs were collected from a cohort of mother-infant pairs and household members <16?years. Pneumococci from 2009 to 2011 were serogrouped using latex agglutination and serotyped by Quellung reaction. In 2014, latex agglutination was used for both steps. Carriage prevalence ratios using prevalence data from before and after vaccine introduction were calculated by log-binomial regression, adjusted for age, seasonality and household composition. Participating infants in 2014 received PCV13 as part of routine immunisation.ResultsVT carriage prior to PCV-13 introduction was 11.4%, 45.1%, 28.2%, 21.2% and 6.6% for 6-week old infants, 18-week old infants, children 1-4?years, children 5-15?years and mothers, respectively. After vaccine introduction, VT carriage decreased among vaccinated 18-week old infants (adjusted prevalence ratio 0.24 (95%CI 0.08-0.75)), vaccinated children 1-4?years (0.54 (0.33-0.88)), unvaccinated children 5-15?years (0.37 (0.17-0.78)) and mothers (0.34 (0.15-0.79)). No decrease in VT carriage was observed for 6-week old infants too young to be vaccinated (1.07 (0.38-3.02)) and PCV-13 ineligible children 1-4?years (0.84 (0.53-1.33)). Non-VT carriage increased only among vaccinated children 1-4?years (1.58 (1.21-2.06)).ConclusionsThere is evidence of reduced VT pneumococcal carriage three years after vaccine introduction in this rural Malawian population with good vaccine coverage using a 3?+?0 schedule. However carriage was sustained among 6-week-old infants and PCV13 ineligible 1-4?year olds, and there was some indication of serotype replacement in vaccinated 1-4?year olds.

Dataset Information

HIV type 1 mutational patterns in HIV type 1 subtype C-infected long-term survivors in Karonga District Malawi: further analysis and correction.

Publications

HIV type 1 mutational patterns in HIV type 1 subtype C-infected long-term survivors in Karonga District Malawi: further analysis and correction.

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