Outcomes in a Cohort of Women Who Discontinued Maternal Triple-Antiretroviral Regimens Initially Used to Prevent Mother-to-Child Transmission during Pregnancy and Breastfeeding—Kenya, 2003–2009

Background

In 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum.

Methods and Findings

The Kisumu Breastfeeding Study, 2003–2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks'' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning–when tARV-PMTCT discontinued–by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P = 0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P = 0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4–40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9–5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing.

Conclusions

Considering the serious health risks to the woman''s infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+.     

Immunological exhaustion: How to make a disparate concept operational?

In this essay, we show that 3 distinct approaches to immunological exhaustion coexist and that they only partially overlap, generating potential misunderstandings. Exploring cases ranging from viral infections to cancer, we propose that it is crucial, for experimental and therapeutic purposes, to clarify these approaches and their interconnections so as to make the concept of exhaustion genuinely operational.     

Early Antenatal Care: Does It Make a Difference to Outcomes of Pregnancy Associated with Syphilis? A Systematic Review and Meta-Analysis

Objective

Despite an increase in the proportion of women who access antenatal care, mother-to-child transmission of syphilis continues to be a consequence of undiagnosed, untreated, or inadequately treated maternal syphilis. We reviewed evidence on the optimal timing of antenatal interventions to prevent mother-to-child transmission of syphilis and its associated adverse outcomes.

Design

Systematic review and meta-analysis of published literature. English-language articles were included if they (1) reported the gestational age at which the mother was screened or tested for syphilis; (2) reported on pregnancy outcome. No publication date limits were set.

Results

We identified a total of 1,199 publications, of which 84 were selected for further review and five were included. All showed a lower prevalence of any adverse outcome among women who received an intervention (to include screening and treatment) in the first and second trimesters of pregnancy compared to the third trimester. The overall odds ratio for any adverse outcome was 2.24 (95% CI 1.28, 3.93). All sub-analyses by type of outcome presented important heterogeneity between studies, except for those studies reporting an infected infant (odds ratio 2.92, 95% CI 0.66, 12.87; I² = 48.2%, p = 0.165).

Conclusions

Our review has shown that the timing of antenatal care interventions makes a significant difference in the risk of having an adverse outcome due to syphilis. Women who sought care in the first two trimesters of their pregnancy, and received the appropriate intervention, were more likely to have a healthy infant, compared to women screened and treated in the third trimester. Encouraging ALL pregnant women to seek care in the first two trimesters of their pregnancy should be a priority for health programmes. For interventions to be effective within these health programmes, health systems and community engagement programmes need to be strengthened to enable pregnant women to seek antenatal care early.     

Vaccination of dogs against Echinococcus granulosus: a means to control hydatid disease?

Hydatid disease continues to be a substantial cause of morbidity and mortality worldwide. Elimination is difficult with current control options, but reducing egg production by Echinococcus granulosus (Eg) in canines might help to reduce transmission in areas where the parasite is endemic. Recently obtained data using recombinant protein-based and live attenuated Salmonella vaccines are preliminary but encouraging and auger well for the future development of an effective dog vaccine against Eg, although much additional work is required before this becomes a reality. New approaches to control and for the prevention of hydatidosis have been described recently, and important additional gains should be expected if the efficacy of the dog vaccines is confirmed and leads to their incorporation into future control options.     

Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg^?1 day^?1) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P?<?0.01) together with a significant elevation (P?<?0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA?+?STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.     

Peptaibiotics and Peptaibols: An Alternative to Classical Antibiotics?

The development and antimicrobial properties of peptaibiotics and peptaibols are discussed. Also, the role of emerging peptaibol analogues, of alamethicin, e.g., harzianins HC, trichotoxin, and antiamoebin, is outlined.     

Asymmetry in Orb-Webs: An Adaptation to Web Building Costs?

Orb-web spiders build vertically asymmetric webs, in which the lower part is larger than the upper part. One hypothesis explaining this asymmetry suggests that the spider’s mass imposes higher building costs in the upper part of the web, causing the spider to reduce this part of the web. We tested this hypothesis by assessing building costs of different parts of the web. We found that the specific time-cost of building (i.e. the time required to build a certain length of silk) differed between the two parts of the web and that the difference in time-costs influenced web asymmetry. Contrary to predictions, however, building costs were larger in the lower part of the web, suggesting that additional factors affect the spider’s decisions while building the web, which are likely to be prey-capture considerations.     

Natural Products: An Alternative to Conventional Therapy for Dermatophytosis?

The increased incidence of fungal infections, associated with the widespread use of antifungal drugs, has resulted in the development of resistance, making it necessary to discover new therapeutic alternatives. Among fungal infections, dermatophytoses constitute a serious public health problem, affecting 20–25 % of the world population. Medicinal plants represent an endless source of bioactive molecules, and their volatile and non-volatile extracts are clearly recognized for being the historical basis of therapeutic health care. Because of this, the research on natural products with antifungal activity against dermatophytes has considerably increased in recent years. However, despite the recognized anti-dermatophytic potential of natural products, often advantageous face to commercial drugs, there is still a long way to go until their use in therapeutics. This review attempts to summarize the current status of anti-dermatophytic natural products, focusing on their mechanism of action, the developed pharmaceutical formulations and their effectiveness in human and animal models of infection.     

Do Strategies to Improve Quality of Maternal and Child Health Care in Lower and Middle Income Countries Lead to Improved Outcomes? A Review of the Evidence

Objectives

Efforts to scale-up maternal and child health services in lower and middle income countries will fail if services delivered are not of good quality. Although there is evidence of strategies to increase the quality of health services, less is known about the way these strategies affect health system goals and outcomes. We conducted a systematic review of the literature to examine this relationship.

Methods

We undertook a search of MEDLINE, SCOPUS and CINAHL databases, limiting the results to studies including strategies specifically aimed at improving quality that also reported a measure of quality and at least one indicator related to health system outcomes. Variation in study methodologies prevented further quantitative analysis; instead we present a narrative review of the evidence.

Findings

Methodologically, the quality of evidence was poor, and dominated by studies of individual facilities. Studies relied heavily on service utilisation as a measure of strategy success, which did not always correspond to improved quality. The majority of studies targeted the competency of staff and adequacy of facilities. No strategies addressed distribution systems, public-private partnership or equity. Key themes identified were the conflict between perceptions of patients and clinical measures of quality and the need for holistic approaches to health system interventions.

Conclusion

Existing evidence linking quality improvement strategies to improved MNCH outcomes is extremely limited. Future research would benefit from the inclusion of more appropriate indicators and additional focus on non-facility determinants of health service quality such as health policy, supply distribution, community acceptability and equity of care.     

En Route to Completion:What Is An Ideal Reference Genome?

<正>Since the Human Genome Project assembled the first draft human genome 20 years ago [1], immense manpower, material,and financial resources have been cast for generating accurate,continuous, complete, and informative reference genome for each important species. Nowadays, although the qualities of these genome assemblies have been significantly improved compared to their initial draft versions,