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  • For most health care professionals infectious disease modell

    2019-04-26

    For most health-care professionals, infectious-disease modelling is something of a black box. One can see the input assumptions (ie, what goes in) and the outputs (ie, what comes out), but what happens in between seems close to magic. Given their complexity, to understand any one of the models used in these studies is difficult; to understand the strengths and limitations of all 11 models might be beyond the capacity of most (if not all) readers. So, we must therefore accept a little magic, and rely on a careful review of what goes in, to decide if what comes out is credible. And the assumed inputs are a major limitation of these studies, for although the involvement of national tuberculosis programme officials in selecting interventions and targets was a strength, the actual population-level effect, and costs, of the interventions are unknown. For example, active case finding through chest radiography was the cornerstone of tuberculosis control for decades in high-income countries, and interest in active case finding has been revived recently. However, scant published evidence of its effect on outcomes, transmission, or its cost-effectiveness is available, and therefore mass screening is not recommended by WHO. The true costs of these interventions, when applied at national scale, are also unknown. Estimations of costs extrapolated from small projects might not be accurate for national-level interventions. For example, the finding that scaling up use of the Xpert RIF/MTB assay might simply reflect better information, since the actual costs for national expansion in South Africa have been carefully measured, by Eosin Y with the estimated costs for the other interventions. Even feasibility is uncertain, particularly for population-level interventions such as mass chest radiography and isoniazid preventive therapy in South Africa, or partnerships with the rapidly evolving private sector in India.
    20 years ago, neonatal survival was not on the global health agenda. In many low-income settings, infants died without recognition, causing untold grief. However, the past two decades have seen steady improvements in neonatal survival on a background of sustained advocacy, a culture of community-based trials, and improvements in quantity and quality of health care, health behaviour, and demand for services. Nevertheless, an annual 2·7 million newborn babies still do not survive their first month of life. Focusing on one intervention to address this issue, two African trials in tested umbilical cord cleansing with antiseptic solution. Supporting evidence to date has come from randomised controlled trials in south Asia, which suggested that cleansing with chlorhexidine solution could reduce both periumbilical inflammation (omphalitis) and neonatal mortality. In a previous Comment we suggested that the putative effects might diminish at scale, that it would be good for families to do the cord cleansing themselves, and that evidence from high-mortality populations in Africa would be helpful. In the interim, a meta-analysis estimated the combined risk ratio (RR) for neonatal mortality at 0·77 (95% CI 0·63–0·94). Katherine Semrau and colleagues did a cluster-randomised controlled trial in Southern Province, Zambia. Fieldworkers visited women antenatally within 24 h of delivery, and repeatedly during the newborns\' first month of life. Families in the intervention group were given 4% chlorhexidine solution to apply 10 mL, using eyedropper bottles, once per day until cord separation, whereas families in the control group were encouraged to maintain dry cord care. Semrau and colleagues reported no difference between allocation groups in the primary outcome of neonatal mortality rate (deaths [in the first 28 days post-partum] per 1000 livebirths; RR 1·12, 95% CI 0·88–1·44) or the secondary outcome of occurrence of omphalitis (diagnosed by erythema or purulent discharge; 0·73, 0·47–1·13). Sunil Sazawal and colleagues did a community-based, individually-randomised controlled trial in Pemba Island, Tanzania. Maternal–child health workers visited on the day of delivery and days 1, 4, 10, and 28; showed families how to care for the cord; and gave them 4% chlorhexidine solution to apply once per day, using 10 mL dropper bottles, until cord separation. The trial began with three comparison groups—dry cord care, chlorhexidine treatment group, or control group using a placebo solution—but the control group was dropped in the second phase of the study. Sazawal and colleagues reported no difference between allocation groups in neonatal mortality rates (RR 0·90, 95% CI 0·74–1·09), but babies in the chlorhexidine group had a lower risk of omphalitis than those in the dry cord care group (0·65, 0·61–0·70). Design and randomisation methods differed between the two studies, but follow-up was exceptionally successful: almost 100% of babies at 28 days in Zambia and 97% in Tanzania. On a spectrum of efficacy, the trials were pitched toward real-world conditions. The interventions were delivered by project staff, but mothers were encouraged to apply the treatment themselves. Whether or not Eosin Y they did so—and it seems likely that they did (98% compliance was reported in the Zambia study)—it was an intention-to-treat approach.