Incidence and determinants of new AIDS-defining illnesses after HAART initiation in a Senegalese cohort

<p>Abstract</p> <p>Background</p> <p>Although a dramatic decrease in AIDS progression has been observed after Highly Active Anti Retroviral Therapy (HAART) in both low- and high-resource settings, few data support that fact in low-resource settings.</p> <p>This study describes the incidence of AIDS-defining illnesses (ADI) after HAART initiation and analyzes their risk factors in a low-resource setting. A focus was put on CD4 cell counts and viral load measurements.</p> <p>Methods</p> <p>404 HIV-1-infected Senegalese adult patients were enrolled in a prospective observational cohort and data censored as of April 2008. A Poisson regression was used to model the incidence of ADIs over two periods and to assess its association with baseline variables, current CD4, current viral load, CD4 response, and virological response.</p> <p>Results</p> <p>ADI incidence declined from 20.5 ADIs per 100 person-years, 95% CI = [16.3;25.8] during the first year to 4.3, 95% CI = [2.3;8.1] during the fourth year but increased afterwards. Before 42 months, the decrease was greater in patients with clinical stage CDC-C at baseline and with a viral load remaining below 1000 cp/mL but was uniform across CD4 strata (p = 0.1). After 42 months, 293 patients were still at risk. The current CD4 and viral load were associated with ADI incidence (decrease of 21% per 50 CD4/mm³and of 61% for patients with a viral load < 1000 cp/mL).</p> <p>Conclusions</p> <p>During the first four years, a uniform decline of ADI incidence was observed even in patients with low CD4-cell counts at HAART initiation as long as the viral load remained undetectable. An increase was noted later in patients with immunologic and virological failures but also in patients with only virological failure.</p

A Trial of the Efficacy, Safety and Impact on Drug Resistance of Four Drug Regimens for Seasonal Intermittent Preventive Treatment for Malaria in Senegalese Children

UNLABELLED: In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. METHODS: 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. FINDINGS: The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. CONCLUSIONS: Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria

Nicotine Promotes Tumor Growth and Metastasis in Mouse Models of Lung Cancer

Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7) nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT) in cultured lung, breast and pancreatic cancer cells. This study demonstrates for the first time that administration of nicotine either by i.p. injection or through over-the-counter dermal patches can promote tumor growth and metastasis in immunocompetent mice. These results suggest that while nicotine has only limited capacity to initiate tumor formation, it can facilitate the progression and metastasis of tumors pre-initiated by tobacco carcinogens

Early biting and insecticide resistance in the malaria vector Anopheles might compromise the effectiveness of vector control intervention in Southwestern Uganda.

BACKGROUND: Southwestern Uganda has high malaria heterogeneity despite moderate vector control and other interventions. Moreover, the early biting transmission and increased resistance to insecticides might compromise strategies relying on vector control. Consequently, monitoring of vector behaviour and insecticide efficacy is needed to assess the effectiveness of strategies aiming at malaria control. This eventually led to an entomological survey in two villages with high malaria prevalence in this region. METHODS: During rainy, 2011 and dry season 2012, mosquitoes were collected in Engari and Kigorogoro, Kazo subcounty, using human landing collection, morning indoor resting collection, pyrethrum spray collection and larval collection. Circumsporozoite protein of Plasmodium falciparum sporozoites in female Anopheles mosquitoes was detected using ELISA assay. Bioassays to monitor Anopheles resistance to insecticides were performed. RESULTS: Of the 1,021 female Anopheles species captured, 62% (632) were Anopheles funestus and 36% (371) were Anopheles gambiae s.l. The most common species were Anopheles gambiae s.l. in Engari (75%) and A. funestus in Kigorogoro (83%). Overall, P. falciparum prevalence was 2.9% by ELISA. The daily entomological inoculation rates were estimated at 0.17 and 0.58 infected bites/person/night during rainy and dry season respectively in Engari, and 0.81 infected bites/person/night in Kigorogoro during dry season. In both areas and seasons, an unusually early evening biting peak was observed between 6 - 8 p.m. In Engari, insecticide bioassays showed 85%, 34% and 12% resistance to DDT during the rainy season, dry season and to deltamethrin during the dry season, respectively. In Kigorogoro, 13% resistance to DDT and to deltamethrin was recorded. There was no resistance observed to bendiocarb and pirimiphos methyl. CONCLUSIONS: The heterogeneity of mosquito distribution, entomological indicators and resistance to insecticides in villages with high malaria prevalence highlight the need for a long-term vector control programme and monitoring of insecticide resistance in Uganda. The early evening biting habits of Anopheles combined with resistance to DDT and deltamethrin observed in this study suggest that use of impregnated bed nets alone is insufficient as a malaria control strategy, urging the need for additional interventions in this area of high transmission

Women experience a better long-term immune recovery and a better survival on HAART in Lao People's Democratic Republic.

<p>Abstract</p> <p>Background</p> <p>In April 2003, Médecins Sans Frontières launched an HIV/AIDS programme to provide free HAART to HIV-infected patients in Laos. Although HIV prevalence is estimated as low in this country, it has been increasing in the last years. This work reports the first results of an observational cohort study and it aims to identify the principal determinants of the CD4 cells evolution and to assess mortality among patients on HAART.</p> <p>Methods</p> <p>We performed a retrospective database analysis on patients initiated on HAART between 2003 and 2009 (CD4<200cells/μL or WHO stage 4). We excluded from the analysis patients who were less than 16 years old and pregnant women. To explore the determinants of the CD4 reconstitution, a linear mixed model was adjusted. To identify typical trajectories of the CD4 cells, a latent trajectory analysis was carried out. Finally, a Cox proportional-hazards model was used to reveal predictors of mortality on HAART including appointment delay greater than 1 day.</p> <p>Results</p> <p>A total of 1365 patients entered the programme and 913 (66.9%) received an HAART with a median CD4 of 49 cells/μL [IQR 15–148]. High baseline CD4 cell count and female gender were associated with a higher CD4 level over time. In addition, this gender difference increased over time. Two typical latent CD4 trajectories were revealed showing that 31% of women against 22% of men followed a high CD4 trajectory. In the long-term, women were more likely to attend appointments without delay. Mortality reached 6.2% (95% CI 4.8-8.0%) at 4 months and 9.1% (95% CI 7.3-11.3%) at 1 year. Female gender (HR=0.17, 95% CI 0.07-0.44) and high CD4 trajectory (HR=0.19, 95% CI 0.08-0.47) were independently associated with a lower death rate.</p> <p>Conclusions</p> <p>Patients who initiated HAART were severely immunocompromised yielding to a high early mortality. In the long-term on HAART, women achieved a better CD4 cells reconstitution than men and were less likely to die. This study highlights important differences between men and women regarding response to HAART and medical care, and questions men’s compliance to treatment.</p

Two Strategies for the Delivery of IPTc in an Area of Seasonal Malaria Transmission in The Gambia: A Randomised Controlled Trial

Bojang and colleagues report a randomized trial showing that delivery of intermittent preventive treatment for malaria in children by village health workers is more effective than delivery by reproductive and child health trekking clinics