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    • Maharaj K Bhan s accompanying Comment correctly identifies t

    2019-05-18

    Maharaj K Bhan\'s accompanying Comment correctly identifies that the main need is to obtain estimates on cause-specific mortality that are specific to each district. In particular, improved understanding is needed of how three causes, which account for 80% of neonatal deaths (birth asphyxia or trauma, low birthweight or prematurity, and infection), and two causes, which account for half of deaths at age 1–59 months (pneumonia and diarrhoea), are distributed among the districts of India. Direct estimates from representative, rapid, and low-cost surveys of cause of death are an emerging global priority for the post-2015 agenda.
    Systematic gender-based neglect and violence has been a chronic social problem encompassing the entire lifespan for women in India. Ram and colleagues (October issue) reiterate this point in their Article indicating higher mortality in girls than in boys younger than 5 years in almost all districts of India, even in high-literacy states. Evidently, decades of policy changes, improved literacy, economic development, and social opportunities for women have not had a major effect. Crime, sexual assaults, and the general climate of violence against women continue to rise in areas where there are skewed sex ratios. Greater societal controls are imposed, especially on women (eg, early marriage and pregnancy, poor maternal nutrition, low literacy, and denial of opportunities for economic mobility). Thus, son preference, and ensuing missing girls, presents an escalating burden in other areas of gender-imbalanced health and safety. Furthermore, son preference also prevails as a cultural problem in some land-owning groups, legitimised by centuries of patriarchal resource control. The psychological notion of masculinity and valuation of female chastity might also be a reason for why women are married early and have lower access to education and nutritional resources. Even though disentanglement of ecological, cultural, and psychological factors is crucial to reduce day-to-day perpetration of gender-based neglect within families, there is no theoretical, evidence-based policy, and targeted implementation framework to do so. Cultural psychological research findings in the communities with male-biased sex ratios suggest that even women prefer sons who have more boys than they corticotropin-releasing factor do sons who have more girls. Women who internalise patriarchal values might continue to practise preferential treatment of sons despite their educational and economic empowerment. At an individual level, internalisation of patriarchal gender beliefs might reduce incentives for academic achievement among girls in these communities.
    Introduction Visceral leishmaniasis is potentially fatal, and causes substantial morbidity in 200 000–400 000 individuals every year, of whom 90% live in the Indian subcontinent. Visceral leishmaniasis causes extreme suffering and financial loss in the poorest populations, who mostly live in remote rural areas. The greatest burden falls on India, with more than 100 000 new cases every year, and Bangladesh, with an estimated 12 440–24 900 new cases per year. In 2005, the Governments of Bangladesh, India, and Nepal committed to eliminate visceral leishmaniasis by 2015. The elimination strategy included the prompt treatment of cases with oral miltefosine. This drug was the only realistic option at the time, despite its potential teratogenicity, risk of non-compliance, and propensity for development of resistant strains. However, after rollout, miltefosine showed an effectiveness of only 83% in a phase 4 trial in Bangladesh, and in Nepal 20% of study participants relapsed after 12 months with a final cure rate of only 79%. These limitations, and the restrictions in the use of miltefosine (it is contraindicated in pregnancy and caution must be taken in women of childbearing age), restricts its use in large-scale programmes. Short-course combination therapy regimens as alternatives to miltefosine—including liposomal amphotericin B plus miltefosine, paromomycin, or miltefosine plus paromomycin—showed promising results in a phase 3 trial in India, but the results of the implementation studies at the primary health-care level will only be available in 2015. The only other option is liposomal amphotericin B (AmBisome, Gilead, USA), which has been shown to be very effective and safe for treatment of visceral leishmaniasis. Previously, the liposomal form was prohibitively expensive for use in control programmes, but, in 2007, Gilead announced a price reduction of 90% (US$18 per 50 mg vial) for all low-income and middle-income countries in which visceral leishmaniasis is endemic. The reduction in price opened up the possibility of use of liposomal amphotericin B in these resource-poor settings. A phase 3 study in India showed an efficacy of 95·7% with a single-dose regimen of liposomal amphotericin B at a dose of 10 mg/kg, with only minor side-effects. However, this study did not report rates of hypersensitivity. This result led to the recent recommendation of the WHO Expert Committee on the Control of Leishmaniasis to use liposomal amphotericin B as a first-line treatment for visceral leishmaniasis in the Indian subcontinent.