Hepatitis B virus infection in lepromatous and tuberculoid patients from Senegal

Hepatitis B Virus (HBV) seric markers (HBs Ag, anti-HBs, and HBe Ag) were studied in 987 Senegalese leprosy patients (lepromatous: LL; tuberculoid: TT) in comparison with 6187 healthy adults (controls). Two populations of leprosy patients from ILAD (Institut de Léprologie Appliquée de Dakar) were studied: The First study (i.e.: study I) between 1973 and 1977 included 553 patients (329 LL; 224 TT). The Second study (i.e.: study II) between 1982 and 1986 included 434 patients (236 LL; 198 TT). HBV serological markers were tested by various techniques. By RIA, they were present in 98% and 96.5% in the studies I and II respectively. Each marker was studied and compared to the control population. HBs Ag detected by RIA was present in 25.5% (study I) and 23.0% (study II) when comparing to 15.2% in the control group. This marker was correlated with leprosy forms (LL and TT), age, sex, ethnic group.     

Molecular analysis of erythrocyte invasion in Plasmodium falciparum isolates from Senegal

The human malaria parasite, Plasmodium falciparum, utilizes multiple ligand-receptor interactions for the invasion of human erythrocytes. Members of the reticulocyte binding protein homolog (PfRh) family have been shown to be critical for directing parasites to alternative erythrocyte receptors that define invasion pathways. Recent studies have identified gene amplification, sequence polymorphism, and variant expression of PfRh paralogs as mechanisms underlying discrimination between pathways for invasion. In this study, we find considerable heterogeneity in the invasion profiles of clonal, uncultured P. falciparum parasite isolates from a low-transmission area in Senegal. Molecular analyses revealed minimal variation in protein expression levels of the PfRh ligands, PfRh1, PfRh2a, and PfRh2b, and an absence of gene amplification in these isolates. However, significant sequence polymorphism was found within repeat regions of PfRh1, PfRh2a, and PfRh2b. Furthermore, we identified a large sequence deletion ( approximately 0.58 kb) in the C-terminal region of the PfRh2b gene at a high prevalence in this population. In contrast to findings of earlier studies, we found no associations between specific sequence variants and distinct invasion pathways. Overall these data highlight the importance of region-specific elaborations in PfRh sequence and expression polymorphisms, which has important implications in our understanding of how the malaria parasite responds to polymorphisms in erythrocyte receptors and/or evades the immune system.     

Removing the regional level from the Niger vaccine supply chain

Objective

Since many of the world's vaccine supply chains contain multiple levels, the question remains of whether removing a level could bring efficiencies.

Methods

We utilized HERMES to generate a detailed discrete-event simulation model of Niger's vaccine supply chain and compared the current four-tier (central, regional, district, and integrated health center levels) with a modified three-tier structure (removing the regional level). Different scenarios explored various accompanying shipping policies and frequencies.

Findings

Removing the regional level and implementing a collection-based shipping policy from the district stores increases vaccine availability from a mean of 70–100% when districts could collect vaccines at least weekly. Alternatively, implementing a delivery-based shipping policy from the central store monthly in three-route and eight-route scenarios only increases vaccine availability to 87%. Restricting central-to district vaccine shipments to a quarterly schedule for three-route and eight-route scenarios reduces vaccine availability to 49%. The collection-based shipping policy from district stores reduces supply chain logistics cost per dose administered from US$0.14 at baseline to US$0.13 after removing the regional level.

Conclusion

Removing the regional level from Niger's vaccine supply chain can substantially improve vaccine availability as long as certain concomitant adjustments to shipping policies and frequencies are implemented.     

Impact of introducing the pneumococcal and rotavirus vaccines into the routine immunization program in Niger

Objectives. We investigated whether introducing the rotavirus and pneumococcal vaccines, which are greatly needed in West Africa, would overwhelm existing supply chains (i.e., the series of steps required to get a vaccine from the manufacturers to the target population) in Niger.Methods. As part of the Bill and Melinda Gates Foundation–funded Vaccine Modeling Initiative, we developed a computational model to determine the impact of introducing these new vaccines to Niger''s Expanded Program on Immunization vaccine supply chain.Results. Introducing either the rotavirus vaccine or the 7-valent pneumococcal conjugate vaccine could overwhelm available storage and transport refrigerator space, creating bottlenecks that would prevent the flow of vaccines down to the clinics. As a result, the availability of all World Health Organization Expanded Program on Immunization vaccines to patients might decrease from an average of 69% to 28.2% (range = 10%–51%). Addition of refrigerator and transport capacity could alleviate this bottleneck.Conclusions. Our results suggest that the effects on the vaccine supply chain should be considered when introducing a new vaccine and that computational models can help assess evolving needs and prevent problems with vaccine delivery.Both rotavirus and pneumococcal disease cause high morbidity and mortality in West African countries. In 2004, more than 65% of deaths associated with rotavirus infection occurred in 11 Asian and African countries. Of these countries, Niger had the highest under-5 mortality (392 deaths/100 000 population younger than 5 years).¹ Each year, Africa alone has 1 to 4 million pneumococcal pneumonia cases, contributing a substantial proportion of the 814 000 annual pneumococcal deaths among children younger than 5 years worldwide.²Although the rotavirus vaccine (RV) and the 7-valent pneumococcal conjugate vaccine (PCV-7) could meet significant needs in West Africa, it is unclear whether the supply chains (i.e., the series of steps required to get a vaccine from the manufacturers to the target population of countries such as Niger) can handle the introduction of these vaccines.³When Merck''s RotaTeq (798 cm³/10-dose box) and GlaxoSmithKline''s Rotarix (259.8 cm³/1-dose box) were introduced in Latin America in 2006 to 2007, these bulky vaccines displaced existing Expanded Programs on Immunization (EPI) vaccines in already limited refrigerator space and forced overburdened health care workers to carry additional thermoses to transport the new vaccines.⁴ To help determine the potential effects on the supply chain of introducing RV or PCV-7 to Niger, the Vaccine Modeling Initiative, funded by the Bill and Melinda Gates Foundation, developed a computational model of the entire Niger vaccine supply chain. We conducted several experiments with different vaccine presentations to explore their effects on storage and transport. We did not consider such resources as buildings, personnel, or vaccine safety injection equipment. We also sought to identify modifications that vaccine policymakers, logisticians, and manufacturers may have to make to facilitate new vaccine introduction.     

Prevalence and risk factors of cervicovaginal HIV shedding among HIV-1 and HIV-2 infected women in Dakar, Senegal

OBJECTIVES: To assess the risk determinants and prevalence of cervicovaginal shedding of HIV-1 and HIV-2 among women in Dakar, Senegal. METHODS: We conducted a cross sectional study of 153 HIV seropositive female sex workers (FSW) and another 142 HIV seropositive women attending an infectious diseases unit, based on an interview, physical examination, and laboratory screening for major sexually transmitted infections (STI). Cervicovaginal lavage fluid was tested for HIV-RNA by means of nested PCR. Links between cervicovaginal shedding of HIV-1 and HIV-2 and sociodemographic, clinical, and laboratory variables were identified by using odd ratios and 95% confidence intervals. Logistic regression analysis was used to identify independent links with HIV shedding. RESULTS: The detection rate of HIV-RNA in cervicovaginal lavage fluid was low among FSW, with no difference between HIV-1 (7/90: 8%) and HIV-2 (3/48: 6%). The rate was far higher among the other women (41%, 48/117; 33%, 7/21 for HIV-1 and HIV-2, respectively). In multivariate analysis, high plasma viral load (>40 000 copies/ml) (AOR = 2.4 (1.0-5.6) p = 0.04) and basic vaginal pH (AOR = 2.2 (1.3-3.7) p = 0.002) were independently associated with HIV-1 shedding. For HIV-2 a CD4 count < 200 cells x 10(6)/l was the only factor associated with the shedding of HIV-2 (AOR = 9.0 (0.9-93)). The genital shedding rate was higher with HIV-1 than with HIV-2 (OR = 2.1 (0.9-4.8), but this difference disappeared after adjustment for the CD4+ cell count (AOR = 1.2 (0.5-2.9)). CONCLUSION: Advanced disease stage and immunosuppression are the major risk determinants for shedding of both HIV-1 and HIV-2. Basic vaginal pH is also a risk determinant for HIV-1 shedding.     

Evolution of the pfcrt T76 and pfmdr1 Y86 markers and chloroquine susceptibility 8 years after cessation of chloroquine use in Pikine, Senegal

The goal of the present study was to assess the evolution of the in vitro chloroquine resistance and also the prevalence of pfcrt T76 and pfmdr1 Y86 mutations in Pikine from 2000 while chloroquine (CQ) was the first-line treatment of malaria to 2009 when artemisinin-based combination therapies (ACTs) are in use. We genotyped pfcrt K76T and pfmdr1 N86Y polymorphisms by PCR-RFLP and assessed in vitro CQ susceptibility by double-site enzyme-linked pLDH immunodetection (DELI) assay in Plasmodium falciparum isolates collected in Pikine, Senegal. The proportions of the pfcrt T76 allele in the light of the three different treatment policies were 72.4?% before CQ withdrawal (2000 to 2003), 47.2?% while amodiaquine plus Fansidar was the first-line treatment (2004 to 2005), and 59.5?% since the ACT use was implemented (2006 to 2009). The prevalence of pfcrt T76 decreased significantly after CQ was stopped [X (2)?=?6.54, P?=?0.01 (2000-2003 versus 2004-2005)] and then slightly since ACTs have been implemented [X (2)?=?1.12, P?=?0.28 (2000-2003 versus 2006-2009)]. There were no significant differences on the prevalence of pfmdr1 Y86 throughout the three treatment policies. The DELI assay was carried out episodically in 2000 (n?=?36), 2001 (n?=?47), and 2009 (n?=?37). The mean IC(50)s of the isolates to CQ in 2000 versus 2009 and 2001 versus 2009 are significantly different (P?相似文献   

Pharmacology and immuno-virologic efficacy of once-a-day HAART in African HIV-infected children: ANRS 12103 phase II trial

Objective

To assess 12-month survival, pharmacokinetics, immunologic and virologic efficacy, tolerance, compliance and drug resistance in HIV-infected children in Bobo-Dioulasso, Burkina Faso, receiving once-daily highly-active antiretroviral therapy as a combination of didanosine (DDI), lamivudine (3TC) and efavirenz (EFV).

Methods

In the ANRS 12103 open phase II trial, HIV-infected children were examined at inclusion and monthly thereafter. CD4+ T-lymphocyte (CD4) count, plasma concentration of ribonucleic acid (RNA) of human immunodeficiency virus type 1 (HIV-1) and haematologic and biochemical parameters were measured at baseline and every trimester. HIV-1 resistance testing was performed in case of viral escape. Drug plasma concentrations were determined with high-performance liquid chromatography.

Findings

From February 2006 to November 2007, 51 children (39% girls) with a mean age of 6.8 years were enrolled and treated for 12 months. At baseline, Z scores for mean weight-for-age and mean height-for-age were −2.01 and −2.12, respectively. Mean CD4% was 9.0. Median plasma HIV-1 RNA viral load was 5.51 log₁₀ copies per millilitre (cp/ml). Two children (3.9%) died and another 11 (22%) suffered 13 severe clinical events. At month 12, mean WAZ had improved by 0.63 (P < 0.001) and mean HAZ by 0.57 (P < 0.001). Mean CD4% had risen to 24 (P < 0.001). Viral load was below 300 RNA cp/ml in 81% of the children; HIV resistance mutations were detected in 11 (21.6%).

Conclusion

The once-a-day combination of DDI + 3TC + EFV is an alternative first-line treatment for HIV-1-infected children. Dose adjustment should further improve efficacy.