Best practices for the care of pregnant people living with TB.

BACKGROUND: Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive.METHODS: Following a systematic review of the literature and the input of a global team of health professionals, a series of best practices for the diagnosis, prevention and treatment of TB during pregnancy were developed.RESULTS: Best practices were developed for each of the following areas: 1) screening and diagnosis; 2) reproductive health services and family planning; 3) treatment of drug-susceptible TB; 4) treatment of rifampicin-resistant/multidrug-resistant TB; 5) compassionate infection control practices; 6) feeding considerations; 7) counseling and support; 8) treatment of TB infection/TB preventive therapy; and 9) research considerations.CONCLUSION: Effective strategies for the care of pregnant people across the TB spectrum are readily achievable and will greatly improve the lives and health of this under-served population.

Pharmacokinetics, Placental and Breast Milk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV.

BACKGROUND: Remarkable progress has been achieved in the identification of HIV infection in pregnant women and in the prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breast milk. We also summarized main safety considerations for in utero and breast milk ARVs exposures in infants. METHODS: We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breast milk transport of ARVs, we selected the studies that provided ratios of maternal to the cord (M:C) plasma and breast milk to maternal plasma (M:P) concentrations, respectively. RESULTS: We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect the dosing of several protease inhibitors during pregnancy and limit the use of several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed the currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breast milk and summarized the effect of pregnancy on placental and of breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs. CONCLUSIONS: Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal, and consequently, fetal ARV exposure. Limited available data suggest that the expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breast milk. The drug transporter's role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.

A systematic review of risk factors for death in adults during and after tuberculosis treatment.

BACKGROUND: Despite effective anti-tuberculosis chemotherapy, case-fatality rates of up to 25% are described in both industrialised and resource-poor settings. An understanding of the factors predisposing to poor outcome may allow the development of adjunctive treatment strategies or closer clinical monitoring in high-risk individuals. OBJECTIVES: To describe the definitions and timing of deaths due to tuberculosis (TB), and the reported range of risk factors for death. METHODS: All electronically available studies investigating risk factors for death in TB patients from 1966 to 2010 were analysed. Included were peer-reviewed reports of cohort, case control or cross-sectional studies with the primary objective of determination of quantitative effect estimates of the relationship between risk factors and death in adults treated for TB. Many studies were limited by their retrospective design, reliance on data from registries and charts, and risk of reporting bias. RESULTS: Most studies reported risk factors for all-cause mortality throughout anti-tuberculosis treatment. In the context of high TB incidence and human immunodeficiency virus (HIV) prevalence, risk factors for death are HIV positivity, advancing immunosuppression, smear-negative disease and malnutrition. In regions of low TB incidence and HIV prevalence, risk factors include non-infective comorbidities, sputum smear-positive disease and alcohol and substance misuse. CONCLUSIONS: There remains a need for prospective clinical studies, particularly with a focus on deaths occurring during the first months of anti-tuberculosis treatment. Qualitative research should be used to further explore the relationship between sex and health-seeking behaviour, and to optimise delivery of health care to socially marginalised groups.

Female reproductive parameters in the Javan gibbon (Hylobates moloch).

Javan gibbons (Hylobates moloch) are one of the most endangered gibbon species in the world. Data on the reproductive biology of the species are almost nonexistent, and a general understanding of the female reproductive biology of this species is important for both ex situ and in situ conservation. Using 18 years of data from 11 captive individuals, we provide new information on the reproductive biology of Javan gibbons based on sexual swelling and menstrual bleeding, including reproductive development, interbirth intervals, and ovarian cycle lengths. Menarche and the onset of sexual swelling occurred at 6.2 and 6.5 years respectively, followed by a period of adolescent sterility of about 1.5 years. Average age at first birth was 8.8 years, and interbirth intervals were about 2.3 years, decreasing to 1.0 year during cases of infant mortality at or shortly after birth. Ovarian cyclicity was measured through periods between menstrual bleeding and sexual swelling. Menstrual bleeding indicates the start of a new ovarian cycle, while sexual swelling normally occurs near the time of ovulation. Menstrual bleeding intervals gave a cycle length of 25.6 days, while sexual swelling intervals gave a cycle length of 27.3 days. These both correspond closely to cycle lengths in other gibbon species, as well as hormonal studies in Javan gibbons. In particular, observing the presence/absence of swellings was found to be a useful and easy method to monitor female ovarian cycles, and could be a practical noninvasive technique for caretakers and researchers.

Intravenous therapy.

Intravenous administration of fluids, drugs, and nutrition is very common in hospitals. Although insertion of peripheral and central cannulae and subsequent intravenous therapy are usually well tolerated, complications that prolong hospitalisation, and in some cases cause death, can arise on occasions. Additionally, many cannulae are inserted unnecessarily. This article seeks to review this area and to outline good medical practice.