Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed

Child care center policies and practices for management of ill children

OBJECTIVES: The objectives of this study were to 1) describe child care staff knowledge and beliefs regarding upper respiratory tract infections and antibiotic indications and 2) evaluate child care staff reported reasons for a) exclusion from child care, b) referral to a health care provider, and c) recommending antibiotics for an ill child. METHODS: A longitudinal study based in randomly selected child care centers in Massachusetts. Staff completed a survey to assess knowledge regarding common infections. For six weeks, staff completed a record of absences each day, describing the reason for an absence, and advice given to the parents regarding exclusion, referral to a health care provider, and obtaining antibiotics. Exclusions for the specific illness/symptom were defined as appropriate or inappropriate based on national guidelines. RESULTS: A large proportion of child care staff incorrectly believed that antibiotics are indicated for bronchitis (80.5%) and green rhinorrhea (80.5%) in children. For 82.2% of absences, the circumstances or reasons for the absence were discussed with a child care staff member. Of 538 absences due to illness that child care staff discussed with parents, there were 45 inappropriate exclusions (8.4% of illnesses discussed), 91 appropriate exclusions (16.9% of illnesses discussed), and 402 cases (74.7%) in which no recommendation for exclusion was made. CONCLUSIONS: Misconceptions regarding the need for antibiotics for URIs are common among child care staff. However, day care staff do not pressure parents to seek medical attention or antibiotics

Praziquantel for the treatment of schistosomiasis during human pregnancy.

In 2014, an estimated 40 million women of reproductive age were infected with Schistosoma haematobium, S. japonicum and/or S. mansoni. In both 2003 and 2006, the World Health Organization (WHO) recommended that all schistosome-infected pregnant and breastfeeding women be offered treatment, with praziquantel, either individually or during treatment campaigns. In 2006, WHO also stated the need for randomized controlled trials to assess the safety and efficacy of such treatment. Some countries have yet to follow the recommendation on treatment and many programme managers and pregnant women in other countries remain reluctant to follow the recommended approach. Since 2006, two randomized controlled trials on the use of praziquantel during pregnancy have been conducted: one against S. mansoni in Uganda and the other against S. japonicum in the Philippines. In these trials, praziquantel treatment of pregnant women had no significant effect on birth weight, appeared safe and caused minimal side-effects that were similar to those seen in treated non-pregnant subjects. Having summarized the encouraging data, on efficacy, pharmacokinetics and safety, from these two trials and reviewed the safety data from non-interventional human studies, we recommend that all countries include pregnant women in praziquantel treatment campaigns. We identify the barriers to the treatment of pregnant women, in countries that already include such women in individual treatments and mass drug administration campaigns, and discuss ways to address these barriers

Paediatric and maternal schistosomiasis: shifting the paradigms.

Background: In endemic areas, schistosomiasis causes both overt and subclinical disease in young children and their mothers, as well as in returned travellers. Sources of data: Key recently published literature. Areas of agreement: An action plan for paediatric schistosomiasis and female genital schistosomiasis (FGS) is needed with expanded access to praziquantel (PZQ) treatment required. Areas of controversy: Schistosomiasis-related morbidity is underappreciated. Present and future demand for PZQ treatment is bottlenecked, imbalanced and inequitable. Current dosing, treatment algorithms and access plans are suboptimal with treatment stalled during pregnancy. Growing points: Raised dosing of PZQ (>40 mg/kg) is being explored in young children. Surveillance of female genital schistosomiasis FGS is increasing. Use of PZQ in pregnancy is safe and preventive chemotherapy guidelines are being revised in morbidity- and transmission-control settings. Areas timely for developing research: Shifting focus of population-level control to individual-case management. Detection and prevention of FGS within general health services and integration of PZQ treatment for women and children in antenatal clinics. Feasibility studies assessing alternative and expanded access to PZQ treatment to at-risk children and mothers and pregnant women

Expanding Praziquantel (PZQ) Access beyond Mass Drug Administration Programs: Paving a Way Forward for a Pediatric PZQ Formulation for Schistosomiasis.

Treating preschool age children (PSAC) with schistosomiasis remains a challenge. Without a pediatric praziquantel (PZQ) formulation, the inclusion of this age group in control programs is limited, and general access to treatment in routine care settings is severely bottlenecked. There are, however, current platforms that target PSAC in primary health care such as the integrated management of childhood illnesses (IMCI), which could integrate PZQ in their portfolio and deliver a pediatric PZQ formulation when available. In addition, other age groups such as school-aged children (SAC) could also benefit from the IMCI’s successful strategy and be treated in health centers using a similar approach. This Viewpoint article reports a summary of a symposium held at the American Society of Tropical Medicine and Hygiene national meeting in 2014 that brought together six experts in different areas in the field of pediatric schistosomiasis to form a working group that could provide recommendations for the inclusion of PSAC in the IMCI and other existing preschool outreach programs. This was to develop and adapt methodologies to fill existing gaps left by current mass drug administration (MDA) programs and synergize efforts for schistosomiasis control more broadly. Foremost, this includes a better definition of subclinical disease in young children to integrate into ICMI guidelines and further demonstration of the benefit of expanded access of treatment to children of all ages by encouraging universal access

Metropolitan Social Environments and Pre-HAART/HAART Era Changes in Mortality Rates (per 10,000 Adult Residents) among Injection Drug Users Living with AIDS

Background Among the largest US metropolitan areas, trends in mortality rates for injection drug users (IDUs) with AIDS vary substantially. Ecosocial, risk environment and dialectical theories suggest many metropolitan areas characteristics that might drive this variation. We assess metropolitan area characteristics associated with decline in mortality rates among IDUs living with AIDS (per 10,000 adult MSA residents) after highly active antiretroviral therapy (HAART) was developed. Methods This is an ecological cohort study of 86 large US metropolitan areas from 1993–2006. The proportional rate of decline in mortality among IDUs diagnosed with AIDS (as a proportion of adult residents) from 1993–1995 to 2004–2006 was the outcome of interest. This rate of decline was modeled as a function of MSA-level variables suggested by ecosocial, risk environment and dialectical theories. In multiple regression analyses, we used 1993–1995 mortality rates to (partially) control for pre-HAART epidemic history and study how other independent variables affected the outcomes. Results In multivariable models, pre-HAART to HAART era increases in ‘hard drug’ arrest rates and higher pre-HAART income inequality were associated with lower relative declines in mortality rates. Pre-HAART per capita health expenditure and drug abuse treatment rates, and pre- to HAART-era increases in HIV counseling and testing rates, were weakly associated with greater decline in AIDS mortality. Conclusions Mortality among IDUs living with AIDS might be decreased by reducing metropolitan income inequality, increasing public health expenditures, and perhaps increasing drug abuse treatment and HIV testing services. Given prior evidence that drug-related arrest rates are associated with higher HIV prevalence rates among IDUs and do not seem to decrease IDU population prevalence, changes in laws and policing practices to reduce such arrests while still protecting public order should be considered

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

Seroprevalence of Cysticercosis in Children and Young Adults Living in a Helminth Endemic Community in Leyte, the Philippines

Cysticercosis is a significant public health problem in countries where pigs are raised for consumption and remains an important cause of neurological disease worldwide. The Philippines is considered an endemic area for cysticercosis because cases in both humans and pigs have been reported; however, epidemiologic information stays limited. We conducted a pilot survey of the seroprevalence of human cysticercosis in a village in Leyte, the Philippines, by measuring antibody specific for Taenia solium cyst-fluid antigen. There were 497 subjects aged 7–30 years in our study and most subjects were infected with one or more helminths. The overall cysticercosis seroprevalence in this population was 24.6% (95% CI: 20.82% ~ 28.58%) with no significant difference based on age, sex, or other helminth coinfection status. Although the sample may not be representative of the whole community, the findings suggest that cysticercosis is a significant, but underrecognized public health concern in the Philippines

ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points

The stereocilia rootlet is a key structure in vertebrate hair cells, anchoring stereocilia firmly into the cell’s cuticular plate and protecting them from overstimulation. Using superresolution microscopy, we show that the ankyrin-repeat protein ANKRD24 concentrates at the stereocilia insertion point, forming a ring at the junction between the lower and upper rootlets. Annular ANKRD24 continues into the lower rootlet, where it surrounds and binds TRIOBP-5, which itself bundles rootlet F-actin. TRIOBP-5 is mislocalized in Ankrd24KO/KO hair cells, and ANKRD24 no longer localizes with rootlets in mice lacking TRIOBP-5; exogenous DsRed–TRIOBP-5 restores endogenous ANKRD24 to rootlets in these mice. Ankrd24KO/KO mice show progressive hearing loss and diminished recovery of auditory function after noise damage, as well as increased susceptibility to overstimulation of the hair bundle. We propose that ANKRD24 bridges the apical plasma membrane with the lower rootlet, maintaining a normal distribution of TRIOBP-5. Together with TRIOBP-5, ANKRD24 organizes rootlets to enable hearing with long-term resilience