Morbidity, mortality, and long-term consequences associated with diarrhoea from Cryptosporidium infection in children younger than 5 years: a meta-analyses study.

BACKGROUND: The protozoan Cryptosporidium is a leading cause of diarrhoea morbidity and mortality in children younger than 5 years. However, the true global burden of Cryptosporidium infection in children younger than 5 years might have been underestimated in previous quantifications because it only took account of the acute effects of diarrhoea. We aimed to demonstrate whether there is a causal relation between Cryptosporidium and childhood growth and, if so, to quantify the associated additional burden. METHODS: The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2016 was a systematic and scientific effort to quantify the morbidity and mortality associated with more than 300 causes of death and disability, including diarrhoea caused by Cryptosporidium infection. We supplemented estimates on the burden of Cryptosporidium in GBD 2016 with findings from a systematic review of published and unpublished cohort studies and a meta-analysis of the effect of childhood diarrhoea caused by Cryptosporidium infection on physical growth. FINDINGS: In 2016, Cryptosporidium infection was the fifth leading diarrhoeal aetiology in children younger than 5 years, and acute infection caused more than 48 000 deaths (95% uncertainty interval [UI] 24 600-81 900) and more than 4·2 million disability-adjusted life-years lost (95% UI 2·2 million-7·2 million). We identified seven data sources from the scientific literature and six individual-level data sources describing the relation between Cryptosporidium and childhood growth. Each episode of diarrhoea caused by Cryptosporidium infection was associated with a decrease in height-for-age Z score (0·049, 95% CI 0·014-0·080), weight-for-age Z score (0·095, 0·055-0·134), and weight-for-height Z score (0·126, 0·057-0·194). We estimated that diarrhoea from Cryptosporidium infection caused an additional 7·85 million disability-adjusted life-years (95% UI 5·42 million-10·11 million) after we accounted for its effect on growth faltering-153% more than that estimated from acute effects alone. INTERPRETATION: Our findings show that the substantial short-term burden of diarrhoea from Cryptosporidium infection on childhood growth and wellbeing is an underestimate of the true burden. Interventions designed to prevent and effectively treat infection in children younger than 5 years will have enormous public health and social development impacts. FUNDING: The Bill & Melinda Gates Foundation.

Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016.

BACKGROUND: Shigella and enterotoxigenic Escherichia coli (ETEC) are bacterial pathogens that are frequently associated with diarrhoeal disease, and are a significant cause of mortality and morbidity worldwide. The Global Burden of Diseases, Injuries, and Risk Factors study 2016 (GBD 2016) is a systematic, scientific effort to quantify the morbidity and mortality due to over 300 causes of death and disability. We aimed to analyse the global burden of shigella and ETEC diarrhoea according to age, sex, geography, and year from 1990 to 2016. METHODS: We modelled shigella and ETEC-related mortality using a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We used a compartmental meta-regression tool to model the incidence of shigella and ETEC, which enforces an association between incidence, prevalence, and remission on the basis of scientific literature, population representative surveys, and health-care data. We calculated 95% uncertainty intervals (UIs) for the point estimates. FINDINGS: Shigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212 438 deaths (95% UI 136 979-326 913) and about 13·2% (9·2-17·4) of all diarrhoea deaths. Shigella was responsible for 63 713 deaths (41 191-93 611) among children younger than 5 years and was frequently associated with diarrhoea across all adult age groups, increasing in elderly people, with broad geographical distribution. ETEC was the eighth leading cause of diarrhoea mortality in 2016 among all age groups, accounting for 51 186 deaths (26 757-83 064) and about 3·2% (1·8-4·7) of diarrhoea deaths. ETEC was responsible for about 4·2% (2·2-6·8) of diarrhoea deaths in children younger than 5 years. INTERPRETATION: The health burden of bacterial diarrhoeal pathogens is difficult to estimate. Despite existing prevention and treatment options, they remain a major cause of morbidity and mortality globally. Additional emphasis by public health officials is needed on a reduction in disease due to shigella and ETEC to reduce disease burden. FUNDING: Bill & Melinda Gates Foundation.

Outcomes of osteomyelitis among patients treated with outpatient parenteral antimicrobial therapy.

PURPOSE: To examine the effects of diabetes, vascular disease, age, and antimicrobial therapy on clinical outcomes, including amputation rates, in patients with osteomyelitis treated in the outpatient setting. METHODS: We performed a retrospective chart review of patients treated with intravenous antimicrobial therapy for osteomyelitis at an outpatient infectious diseases practice. All patients were followed for at least 6 months. RESULTS: Four hundred and fifty-four patients qualified for inclusion, with follow-up information available for up to 10 years. One hundred and thirty-nine patients (31%) had recurrences and 27 (6%) had amputations. Of the recurrences, 108 (78%) occurred within 6 months and 132 (95%) within 1 year. In univariate analyses, peripheral vascular disease, diabetes, and the combination were all associated with the risk of recurrence; age (>70 years) was not. For osteomyelitis due to Staphylococcus aureus, the relative risk of recurrence, using a Cox regression model, was 0.8 for ceftriaxone (95% confidence interval [CI]: 0.4 to 1.5; P = 0.53), 1.1 for cefazolin (95% CI: 0.5 to 2.2; P = 0.80), and 2.5 for vancomycin (95% CI: 1.1 to 5.6; P = 0.04), as compared with the use of a penicillinase-resistant penicillin. CONCLUSION: Diabetes and peripheral vascular disease are important factors in determining the prognosis of patients with osteomyelitis, but age is not. Almost all recurrences of osteomyelitis occur within 1 year. Recurrence rates with osteomyelitis associated with S. aureus appear to be higher with the use of vancomycin, whereas ceftriaxone and cefazolin appear to be similar to penicillinase-resistant penicillins.

Risk factors and treatment outcomes in osteomyelitis.

Outcome indicators of recurrence and amputation were used to evaluate risk factors and treatment choices in 454 patients with osteomyelitis who completed outpatient parenteral antimicrobial therapy (OPAT). Three hundred and fifteen (69.4%) were apparently cured at the time outcomes were measured and 139 (30.6%) had a recurrence. Of the recurrences, 56% occurred within 3 months, 78% within 6 months and 95% within 1 year. Both the initial pathogen and the choice of antibiotic had an effect on the risk of treatment failure. Osteomyelitis caused by Pseudomonas aeruginosa was associated with more than a two-fold increase in recurrence (P = 0.005) compared with infection caused by Staphylococcus aureus. There was a positive correlation between P. aeruginosa and amputation. With S. aureus infections, the risk of recurrence was more than twice as great with vancomycin therapy as opposed to treatment with beta-lactams (P = 0.03). Treatment with ceftriaxone was as effective as the penicillinase-resistant penicillins and cefazolin.

Lack of hepatotoxicity associated with nonnucleoside reverse transcriptase inhibitors.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV.