MSIDP Newsletter: New highly productive sorghum varieties released

The Department of Agricultural Research Services (DARS) in partnership with the International Crop research Institute for the Semi-Arid Tropics (ICRISAT), has released three improved sorghum varieties; Pilira 3, Pilira 4 and Pilira 5. These new varieties replace Pilira 1 and Pilira 2, released in 1993, and have since been the only improved sorghum varieties available in Malawi

Evaluation of host serum protein biomarkers of tuberculosis in sub-Saharan Africa

Accurate and affordable point-of-care diagnostics for tuberculosis (TB) are needed. Host serum protein signatures have been derived for use in primary care settings, however validation of these in secondary care settings is lacking. We evaluated serum protein biomarkers discovered in primary care cohorts from Africa reapplied to patients from secondary care. In this nested case-control study, concentrations of 22 proteins were quantified in sera from 292 patients from Malawi and South Africa who presented predominantly to secondary care. Recruitment was based upon intention of local clinicians to test for TB. The case definition for TB was culture positivity for Mycobacterium tuberculosis; and for other diseases (OD) a confirmed alternative diagnosis. Equal numbers of TB and OD patients were selected. Within each group, there were equal numbers with and without HIV and from each site. Patients were split into training and test sets for biosignature discovery. A nine-protein signature to distinguish TB from OD was discovered comprising fibrinogen, alpha-2-macroglobulin, CRP, MMP-9, transthyretin, complement factor H, IFN-gamma, IP-10, and TNF-alpha. This signature had an area under the receiver operating characteristic curve in the training set of 90% (95% CI 86–95%), and, after adjusting the cut-off for increased sensitivity, a sensitivity and specificity in the test set of 92% (95% CI 80–98%) and 71% (95% CI 56–84%), respectively. The best single biomarker was complement factor H [area under the receiver operating characteristic curve 70% (95% CI 64–76%)]. Biosignatures consisting of host serum proteins may function as point-of-care screening tests for TB in African hospitals. Complement factor H is identified as a new biomarker for such signatures

Pharmacokinetics of generic and trade formulations of lamivudine, stavudine and nevirapine in HIV-infected Malawian children

Evaluate the pharmacokinetics (PK) of lamivudine (3TC), stavudine (d4T), and nevirapine (NVP) in HIV-infected Malawian children receiving quartered tablet multiples of Triomune 40™ (GT) compared to individual generic (GL) and trade (TL) liquid

CD209 Genetic Polymorphism and Tuberculosis Disease

BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2 x 2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. CONCLUSION: This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response

Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted—The Breastfeeding, Antiretrovirals, and Nutrition Study

Antiretroviral interventions are used to reduce HIV viral replication and prevent mother-to-child transmission. Viral suppression relies on adherence to antiretrovirals

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women

Background: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings

Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission

Estimate association between postpartum antiretroviral adherence and breastmilk HIV-1 transmissio

Human immunodeficiency virus increases the risk of tuberculosis due to recent re-infection in individuals with latent infection.

BACKGROUND: Human immunodeficiency virus associated tuberculosis (TB) disease can follow reactivation of latent Mycobacterium tuberculosis infection or recent (re-)infection with M. tuberculosis. If contemporary TB cases share identical M. tuberculosis strains (i.e., are 'clustered'), the episode is likely to have followed recent (re-)infection, irrespective of evidence of previous latent infection. METHODS: Individuals experiencing a first TB episode between 1996 and 2008 in Karonga District, Northern Malawi, were included if information on M. tuberculosis infection status (from tuberculin tests) before 1990 and a DNA fingerprint from the TB episode were available. We explored differences in proportion clustered by prior M. tuberculosis infection status and HIV status, adjusting for age, sex, bacille Calmette-Guérin scar status and time since tuberculin testing. RESULTS: Of 79 HIV-negative TB cases, those with previous M. tuberculosis infection were much less likely to be clustered than cases without prior infection (29% vs. 77%, adjusted OR = 0.15, 95%CI 0.04-0.59). Among 119 HIV-positive TB cases, clustering was similar in both groups (88% vs. 84%, adjusted OR = 1.85, 95%CI 0.41-8.29). DISCUSSION: HIV infection appears to increase the risk of TB following recent re-infection in patients with latent M. tuberculosis infection. Our results add to the mounting evidence that HIV-associated TB mainly follows recent M. tuberculosis infection

Patterns and implications of naturally acquired immune responses to environmental and tuberculous mycobacterial antigens in northern Malawi.

Interferon (IFN)-gamma responsiveness to 12 purified protein derivative (PPD) and new tuberculin antigens from 9 species of mycobacteria was assessed, using a whole blood assay, in 616 young adults living in northern Malawi, where Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination provides no protection against pulmonary tuberculosis. The prevalence of IFN-gamma responsiveness was highest for PPDs of M. avium, M. intracellulare, and M. scrofulaceum (the MAIS complex). Correlations between responsiveness paralleled genetic relatedness of the mycobacterial species. A randomized, controlled trial was carried out, to assess the increase in IFN-gamma responsiveness to M. tuberculosis PPD that can be attributed to M. bovis BCG vaccination. The BCG-attributable increase in IFN-gamma response to M. tuberculosis PPD was greater for individuals with low initial responsiveness to MAIS antigens than for those with high initial responsiveness. Although not statistically significant, the trend is consistent with the hypothesis that prior exposure to environmental mycobacteria interferes with immune responses to BCG vaccination

The influence of prior exposure to environmental mycobacteria on the IFN-(gamma) response to BCG vaccination in southern England and northern Malaw

We report a large study of the effect of BCG vaccination on the in vitro 6-day whole blood interferon-gamma (IFN-γ) response to antigens from eight species of mycobacteria among schoolchildren in south-eastern England, where bacille Calmette–Guérin (BCG) vaccination is highly protective against pulmonary tuberculosis, and among young adults in northern Malawi, where BCG vaccination is not protective. In the UK children, BCG induced an appreciable increase in IFN-γ response to antigens from most species of mycobacteria. The degree of change was linked to the relatedness of the species to Mycobacterium bovis BCG, and provides further evidence of the cross-reactivity of mycobacterial species in priming of the immune system. IFN-γ responses to purified protein derivatives (PPDs) from M. tuberculosis and environmental mycobacteria were more prevalent in the Malawian than the UK group prior to vaccination; BCG vaccination increased the prevalence of responses to these PPDs in the UK group to a level similar to that in Malawi. There was no evidence that the vaccine-induced change in IFN-γ response was dependent upon the magnitude of the initial response of the individual to environmental mycobacteria in the United Kingdom or in Malawi. These observations should assist the development and interpretation of human clinical trials of new vaccines against M. tuberculosis in areas of both low and high exposure to environmental mycobacteria