Inadequate lopinavir concentrations with modified 8-hourly lopinavir/ritonavir 4:1 dosing during rifampicin-based tuberculosis treatment in children living with HIV

BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment. METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment. RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L. CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis treatment are of concern and requires further evaluation

Balanced dynamics for three dimensional curved flows

Spring 1993.Includes bibliographical references.Sponsored by the National Science Foundation ATM-9115485

Bark removal for medicinal use predisposes indigenous forest trees to wood degradation in Zambia

Bark harvesting for medicinal purposes has become widespread in Zambia, mainly due to the high levels of poverty among the population. The injury caused to trees leads to wood deterioration as a result of insect damage and fungal infection. This study aimed to ascertain the effects of different bark harvesting practices on the quality of wood of selected indigenous tree species often used as medicinal plants. The bark of these trees, which included Julbernardia paniculata, Isoberlinia angolensis, Brachystegia longifolia, Albizia adianthifolia and Parinari curatellifolia, was removed by (1) stripping bark on the side of the tree facing the sun, (2) on the shaded side of the tree, (3) covering the wound with mud immediately after harvesting, (4) stripping at night and (5) no wounding as control. Wood of J. paniculata and I. angolensis was severely deteriorated, displaying extensive tissue discolouration, increased insect infestation and profuse gum exudation, especially when the wound was not covered with mud. Covering the wound site with mud considerably protected the trees from wood deterioration and insect damage and this constitutes the best and most sustainable bark harvesting prescription for biodiversity conservation. Keywords: Africa, Albizia adianthifolia, bark harvesting, Brachystegia longifolia, Isoberlinia angolensis, Julbernardia paniculata, Parinari curatellifolia, tree wounds, wood deteriorationSouthern Hemisphere Forestry Journal 2007, 69(3): 157–16

Tsotsies are disturbing the normal way of life

A morality song about the tsotsies accompanied by guitar

Because of Castle beer, people go naked

A morality song about people spending money on beer accompanied by guitar

Questing activity of Rhipicephalus appendiculatus (Acari: Ixodidae) nymphs: a random process?

In Zambia, an experiment under quasi-natural conditions indicated that Rhipicephalus appendiculatus nymphs react to prevailing climatic conditions. Higher temperatures and higher vapour pressure deficits lead to decreased activity. The majority of nymphs (>75%) were recorded at ground level. Simulations showed that larval phenology and temperature during the nymphal premoulting period largely explain the seasonal abundance patterns of nymphs, as observed on cattle, given the absence of a behavioural diapause. Consequently, the effect of climate, as observed in our studies, is masked. However, the results of the present study indicate that daily climatic conditions probably have a much larger effect on the transmission dynamics of Theileria parva. The vertical distribution of questing instars is a function of temperature and humidity. In years of unfavourable conditions, nymphs might feed mainly on hosts other than cattle, and this could govern the infection prevalence in the adult population. This suggestion is supported by previous epidemiological studies

The proportion of all TB notifications that are accounted for by childhood notifications according to intervention and control sites.

The proportion of all TB notifications that are accounted for by childhood notifications according to intervention and control sites.</p

Geographical locations of intervention and control sites under the study.

Geographical locations of intervention and control sites under the study.</p

Childhood TB notifications before and during implementation of strategy to improve TB detection among children by intervention and control sites.

Childhood TB notifications before and during implementation of strategy to improve TB detection among children by intervention and control sites.</p

Manuscript data.

IntroductionIn high TB burden settings, it is estimated that 10–20% of total notifications should be children, however, currently only 6–8% of the total TB notifications in Zambia are children. We assessed whether the implementation of a multicomponent strategy, at primary healthcare facilities, that systematically targets barriers at each step of the childhood TB diagnostic cascade can increase childhood TB case detection.MethodsWe conducted a controlled, interrupted time series analysis to compare childhood TB case notifications before (January 2018—December 2019), and during implementation (January 2020—September 2021) in two intervention and two control Level 1 hospitals in Lusaka, Zambia. At each of the intervention facilities, we implemented a multicomponent strategy constituting: (1) capacity development on childhood TB and interpretation of chest x-ray, (2) TB awareness-raising and demand creation activities, (3) setting up fast track TB services, (4) strengthening of household contact tracing, and (5) improving access to digital chest X-ray for TB screening and Xpert MTB/Rif Ultra for TB diagnosis, through strengthening sample collection in children.FindingsAmong 5,150 children ConclusionA standardized package of strategies to improve childhood TB detection at primary healthcare facilities was feasible to implement and was associated with a sustained improvement in childhood TB notifications.</div