Investigation of a combination of amiodarone and itraconazole for treatment of American trypanosomiasis (Chagas disease) in dogs.

OBJECTIVE: To evaluate clinical, serologic, parasitological, and histologic outcomes of dogs with naturally occurring Trypanosoma cruzi infection treated for 12 months with amiodarone and itraconazole. ANIMALS: 121 dogs from southern Texas and southern Louisiana. PROCEDURES: Treatment group dogs (n = 105) received a combination of amiodarone hydrochloride (approx 7.5 mg/kg [3.4 mg/lb], PO, q 24 h, with or without a loading dosage protocol) and itraconazole (approx 10 mg/kg [4.5 mg/lb], PO, q 24 h, adjusted to maintain a plasma concentration of 1 to 2 µg/mL) for 12 months. Control group dogs (n = 16) received no antitrypanosomal medications. Serologic assays for anti-T cruzi antibodies, PCR assays for T cruzi DNA in blood, and physical evaluations were performed 1, 6, 9, 12, and 24 months after study initiation. Adverse events were recorded. Outcomes of interest were recorded and compared between groups. RESULTS: 86 of 105 treatment group dogs and 8 of 16 control group dogs survived and completed the study (5/19 and 6/7 deaths of treatment and control group dogs, respectively, were attributed to T cruzi infection). Mean survival time until death attributed to T cruzi was longer (23.19 vs 15.64 months) for the treatment group. Results of PCR assays were negative for all (n = 92) tested treatment group dogs (except for 1 dog at 1 time point) from 6 to 24 months after study initiation. Clinical improvement in ≥ 1 clinical sign was observed in 53 of 54 and 0 of 10 treatment and control group dogs, respectively; adverse drug events were minor and reversible. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested efficacy of this trypanocidal drug combination for the treatment of T cruzi infection in dogs.

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect.