A high-resolution map of the Grp1 locus on chromosome V of potato harbouring broad-spectrum resistance to the cyst nematode species Globodera pallida and Globodera rostochiensis

The Grp1 locus confers broad-spectrum resistance to the potato cyst nematode species Globodera pallida and Globodera rostochiensis and is located in the GP21-GP179 interval on the short arm of chromosome V of potato. A high-resolution map has been developed using the diploid mapping population RHAM026, comprising 1,536 genotypes. The flanking markers GP21 and GP179 have been used to screen the 1,536 genotypes for recombination events. Interval mapping of the resistances to G. pallida Pa2 and G. rostochiensis Ro5 resulted in two nearly identical LOD graphs with the highest LOD score just north of marker TG432. Detailed analysis of the 44 recombinant genotypes showed that G. pallida and G. rostochiensis resistance could not be separated and map to the same location between marker SPUD838 and TG432. It is suggested that the quantitative resistance to both nematode species at the Grp1 locus is mediated by one or more tightly linked R genes that might belong to the NBS-LRR class

A genome-wide genetic map of NB-LRR disease resistance loci in potato

Like all plants, potato has evolved a surveillance system consisting of a large array of genes encoding for immune receptors that confer resistance to pathogens and pests. The majority of these so-called resistance or R proteins belong to the super-family that harbour a nucleotide binding and a leucine-rich-repeat domain (NB-LRR). Here, sequence information of the conserved NB domain was used to investigate the genome-wide genetic distribution of the NB-LRR resistance gene loci in potato. We analysed the sequences of 288 unique BAC clones selected using filter hybridisation screening of a BAC library of the diploid potato clone RH89-039-16 (S. tuberosum ssp. tuberosum) and a physical map of this BAC library. This resulted in the identification of 738 partial and full-length NB-LRR sequences. Based on homology of these sequences with known resistance genes, 280 and 448 sequences were classified as TIR-NB-LRR (TNL) and CC-NB-LRR (CNL) sequences, respectively. Genetic mapping revealed the presence of 15 TNL and 32 CNL loci. Thirty-six are novel, while three TNL loci and eight CNL loci are syntenic with previously identified functional resistance genes. The genetic map was complemented with 68 universal CAPS markers and 82 disease resistance trait loci described in literature, providing an excellent template for genetic studies and applied research in potato

Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

OBJECTIVE: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort. DESIGN: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. METHODS: Adults initiating ART 1(st) August 2004-31(st) October 2009 were stratified by age at initiation: young adults (16-24 years) mid-age adults (25-49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. RESULTS: 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25-49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90-7.78); 6.55 (95% CI 6.11-7.02) and 8.69 (95% CI 7.34-10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36) and 3-12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months) whilst immunological and virological responses were associated with mortality after 12 months. CONCLUSIONS: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART

Impact of Simian Immunodeficiency Virus Infection on Chimpanzee Population Dynamics

Like human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002–2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of −6.5% to −7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002–2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen

Aetiology of sexually transmitted infections and response to syndromic treatment in southwest Uganda.

OBJECTIVE: To determine the aetiology of genital ulcers and discharges in rural south western Uganda and to assess response to syndromic treatment. METHOD: A longitudinal, prospective study using laboratory testing and questionnaires to evaluate 561 adult men and women presenting with clinically verified genital ulcers, urethral, or vaginal discharge at a general outpatient clinic and two health centres between December 1999 and July 2001. RESULTS: One third of patients had genital ulcers and two thirds discharges. There was good response to treatment in 461/508 patients (90.7%). Herpes simplex virus type 2 was found in 95/217 (43.8%) genital ulcers. In 24.1% of ulcer cases there was also a genital discharge. HIV seropositivity was high in ulcer cases (63.2%), with significantly more HSV2 and secondary bacterial infection than in seronegative cases. Neisseria gonorrhoeae was found in 135/204 (66.2%) male genital discharges. Female genital discharges were mostly associated with bacterial vaginosis (36.1%), Trichomonas vaginalis (18.9%), and candidiasis (18.6%). CONCLUSIONS: The aetiological pattern of STI syndromes reported will help inform revision of national STI guidelines. The importance of herpes simplex virus type 2, the variation in causes of genital ulcers according to HIV serostatus, the high frequency of multiple infections and secondary bacterial contamination of genital ulcers are notable. These results help explain the lack of effect of an STI intervention on HIV incidence in a recent trial in this area

Estimation of the HIV basic reproduction number in rural south west Uganda: 1991-2008.

BACKGROUND: The basic reproduction number, [Formula: see text], is one of the many measures of the epidemic potential of an infection in a population. We estimate HIV [Formula: see text] over 18 years in a rural population in Uganda, examine method-specific differences in estimated [Formula: see text], and estimate behavioural changes that would reduce [Formula: see text] below one. METHODS: Data on HIV natural history and infectiousness were collated from literature. Data on new sexual partner count were available from a rural clinical cohort in Uganda over 1991-2008. [Formula: see text] was estimated using six methods. Behavioural changes required to reduce [Formula: see text] below one were calculated. RESULTS: Reported number of new partners per year was 0 to 16 (women) and 0 to 80 (men). When proportionate sexual mixing was assumed, the different methods yielded comparable [Formula: see text] estimates. Assuming totally assortative mixing led to increased [Formula: see text] estimates in the high sexual activity class while all estimates in the low-activity class were below one. Using the "effective" partner change rate introduced by Anderson and colleagues resulted in [Formula: see text] estimates all above one except in the lowest sexual activity class. [Formula: see text] could be reduced below one if: (a) medium risk individuals reduce their partner acquisition rate by 70% and higher risk individuals reduce their partner acquisition rate by 93%, or (b) higher risk individuals reduce the partner acquisition rate by 95%. CONCLUSIONS: The estimated [Formula: see text] depended strongly on the method used. Ignoring variation in sexual activity leads to an underestimation of [Formula: see text]. Relying on behaviour change alone to eradicate HIV may require unrealistically large reductions in risk behaviour, even though for a small proportion of the population. To control HIV, complementary prevention strategies such as male circumcision and HIV treatment services need rapid scale up

Mortality and its predictors among antiretroviral therapy naïve HIV-infected individuals with CD4 cell count ≥350 cells/mm(3) compared to the general population: data from a population-based prospective HIV cohort in Uganda.

BACKGROUND: Evidence exists that even at high CD4 counts, mortality among HIV-infected antiretroviral therapy (ART) naïve individuals is higher than that in the general population. However, many developing countries still initiate ART at CD4 ≤350 cells/mm(3). OBJECTIVE: To compare mortality among HIV-infected ART naïve individuals with CD4 counts ≥350 cells/mm(3) with mortality in the general Ugandan population and to investigate risk factors for death. DESIGN: Population-based prospective HIV cohort. METHODS: The study population consisted of HIV-infected people in rural southwest Uganda. Patients were reviewed at the study clinic every 3 months. CD4 cell count was measured every 6 months. Rate ratios were estimated using Poisson regression. Indirect methods were used to calculate standardised mortality ratios (SMRs). RESULTS: A total of 374 participants with CD4 ≥350 cells/mm(3) were followed for 1,328 person-years (PY) over which 27 deaths occurred. Mortality rates (MRs) (per 1,000 PY) were 20.34 (95% CI: 13.95-29.66) among all participants and 16.43 (10.48-25.75) among participants aged 15-49 years. Mortality was higher in periods during which participants had CD4 350-499 cells/mm(3) than during periods of CD4 ≥500 cells/mm(3) although the difference was not statistically significant [adjusted rate ratio (aRR)=1.52; 95% CI: 0.71-3.25]. Compared to the general Ugandan population aged 15-49 years, MRs were 123% higher among participants with CD4 ≥500 cells/mm(3) (SMR: 223%, 95% CI: 127-393%) and 146% higher among participants with CD4 350-499 cells/mm(3) (246%, 117%-516). After adjusting for current age, mortality was associated with increasing WHO clinical stage (aRR comparing stage 3 or 4 and stage 1: 10.18, 95% CI: 3.82-27.15) and decreasing body mass index (BMI) (aRR comparing categories ≤17.4 Kg/m(2) and ≥18.5 Kg/m(2): 6.11, 2.30-16.20). CONCLUSION: HIV-infected ART naïve individuals with CD4 count ≥350 cells/mm(3) had a higher mortality than the general population. After adjusting for age, the main predictors of mortality were WHO clinical stage and BMI