Summit proceedings: Biomedical countermeasure development for emerging vector-borne viral diseases.

Emerging and re-emerging infectious diseases are an expanding global threat to public health, security, and economies. Increasing populations, urbanization, deforestation, climate change, anti-vaccination movements, war, and international travel are some of the contributing factors to this trend. The recent Ebola, MERS-CoV, and Zika outbreaks demonstrated we are insufficiently prepared to respond with proven safe and effective countermeasures (i.e., vaccines and therapeutics). The State University of New York Upstate Medical University and the Trudeau Institute convened a summit of key opinion and thought leaders in the life sciences and biomedical research and development enterprises to explore global biopreparedness challenges, take an inventory of existing capabilities and capacities related to preparation and response, assess current "gaps," and prospect what could be done to improve our position. Herein we describe the summit proceedings, "Translational Immunology Supporting Biomedical Countermeasure Development for Emerging Vector-borne Viral Diseases," held October 2-3, 2018, at the Trudeau Institute in Saranac Lake, NY.

Prevalence of undiagnosed asymptomatic bacteriuria and associated risk factors during pregnancy: a cross-sectional study at two tertiary centres in Cairo, Egypt.

BACKGROUND: The prevalence of asymptomatic bacteriuria (ASB) during pregnancy is poorly understood in Egypt-a country with a high birth rate. OBJECTIVES: To determine the prevalence of ASB among pregnant women booking at El Hussein and Sayed Galal Hospitals in Al-Azhar University in Egypt; and to observe the relationship between ASB prevalence and risk factors such as socioeconomic level and personal hygiene. SETTING: Obstetrics and gynaecology clinics of 2 university hospitals in the capital of Egypt. Both hospitals are teaching and referral hospitals receiving referrals from across over the country. They operate specialist antenatal clinics 6 days per week. PARTICIPANTS: A cross-sectional study combining the use of questionnaires and laboratory analysis was conducted in 171 pregnant women with no signs or symptoms of urinary tract infection (1 case was excluded). Samples of clean catch midstream urine were collected and cultured using quantitative urine culture and antibiotic sensitivity tests were performed. RESULTS: Of 171 pregnant women, 1 case was excluded; 17 cases (10%, 95% CI 5.93% to 15.53%) were positive for ASB. There was a statistically significant relation between the direction of washing genitals and sexual activity per week-and ASB. Escherichia coli was the most commonly isolated bacteria followed by Klebsiella. Nitrofurantoin showed 100% sensitivity, while 88% of the isolates were resistant to cephalexin. CONCLUSIONS: The prevalence of ASB seen in pregnant women in 2 tertiary hospitals in Egypt was 10%. E. coli and Klebsiella are the common organisms isolated. The direction of washing genitals and sexual activity significantly influences the risk of ASB. Pregnant women should be screened early for ASB during pregnancy; appropriate treatment should be given for positive cases according to antibiotic sensitivity screening. Cephalexin is likely to be of limited use in this management.

Targeting rubella for elimination.

Rubella is an acute, usually mild viral disease. However, when rubella infection occurs just before conception or during the first 8-10 weeks of gestation, it causes multiple fetal defects in up to 90% of cases, known as Congenital Rubella Syndrome (CRS). It may result in fetal wastage, stillbirths and sensorineural hearing deficit up to 20 weeks of gestation. Rubella vaccine (RA 27/3) is highly effective and has resulted in elimination of rubella and CRS from the western hemisphere and several European countries. Review of several studies documents the duration of protection over 10-21 years following one dose of RA27/3 vaccination, and persistent seropositivity in over 95% cases. Studies in India show seronegativity to rubella among adolescent girls to vary from 10% to 36%. Although due to early age of infection resulting in protection in the reproductive age group, incidence of rubella in India is not very high. However, due to severity of CRS coupled with introduction of RCV in private sector and in some of the states which is likely to lead to sub-optimal coverage and resulting higher risk of rubella during pregnancy in the coming decades, it is imperative to adopt the goal of rubella elimination. As in order to control measles, the country has adopted strategy of delivering second dose of measles through measles campaigns covering children 9 months to 10 years of age in 14 states, it is recommended to synergize efforts for elimination of rubella with these campaigns by replacing measles vaccine by MR or MMR vaccine. Other states which are to give second dose of measles through routine immunization will also have to adopt campaign mode in order to eliminate rubella from the country over 10-20 years. Subsequently, measles vaccine can be replaced by MR or MMR vaccine in the national schedule.

Vitamin D status and its association with morbidity including wasting and opportunistic illnesses in HIV-infected women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings.

Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis.

OBJECTIVE: Recent data suggest vitamin D deficiency (VDD) is associated with bacterial vaginosis (BV) during pregnancy. We hypothesized that VDD is a risk factor for BV in nonpregnant women. STUDY DESIGN: Using National Health and Nutrition Examination Survey data, we conducted multivariable logistic regression analyses stratified by pregnancy. RESULTS: VDD was associated with BV only in pregnant women (adjusted odds ratio [AOR], 2.87; 95% confidence interval [CI], 1.13-7.28). Among nonpregnant women, douching (AOR, 1.72; 95% CI, 1.25-2.37), smoking (AOR, 1.66; 95% CI, 1.23-2.24), and black race (AOR, 2.41; 95% CI, 1.67-3.47) were associated with BV; oral contraceptive use was inversely associated with BV (AOR, 0.60; 95% CI, 0.40-0.90). VDD moderated the association between smoking and BV in nonpregnant women. CONCLUSION: Risk factors for BV differ by pregnancy status. VDD was a modifiable risk factor for BV among pregnant women; evaluation of vitamin D supplementation for prevention or adjunct therapy of BV in pregnancy is warranted.

Knowledge of, and attitudes to, acquired immune deficiency syndrome (AIDS) among traditional birth attendants (TBAs) in rural communities in Cross River State, Nigeria.

AIM: To survey knowledge of, and attitudes to, HIV/AIDS held by traditional birth attendants (TBAs) in rural communities in Cross River State, Nigeria. BACKGROUND: As the HIV/AIDS epidemic continues to spread, undermining development, reversing health gains and exacerbating poverty, TBAs in rural communities in Cross River State, Nigeria are still less informed about this dreadful disease. METHODS: A survey consisting of structured questionnaires was used with 140 randomly selected TBAs to assess their knowledge of HIV/AIDS, source of information on HIV and protective practices. FINDINGS: Results revealed that 62 (44.3%) of the TBAs had no formal education. Forty-four (31.4%) had primary education, while 19 (13.6%) had secondary education. On knowledge of HIV and sources of information, 49 (35.0%) of respondents reported knowing what HIV means. While 26.4% indicated that they received information about HIV from the government health centres, 23.6% had no information about the disease. There was a great disparity between male (73.7%) and female (28.9%) respondents on knowledge about HIV. On the use of protective safety procedures during delivery, 61 (43.6%) used sterilized blades, while 10.7% admitted wearing protective clothes and gloves. Only three (2.1%) of the respondents said that they were aware of the HIV status of their clients prior to delivery. CONCLUSIONS: This survey has demonstrated that few TBAs in the communities studied in Cross River State are informed about HIV/AIDS, and this has revealed the urgency of starting a programme specifically designed for TBAs in rural communities towards a massive educational campaign on HIV/AIDS.

Incidence of neonatal herpes simplex virus infections in a managed-care population.

OBJECTIVE: To determine the incidence of possible neonatal herpes simplex virus (HSV) infections, HSV infection status of women with infected infants, and use of measures to reduce risk of HSV transmission to the neonate in a large US managed-care population. STUDY DESIGN: Retrospective analysis of administrative claims from the Integrated Health Care Information Services National Managed Care Benchmark database. RESULTS: Of 233,487 infants born to 252,474 mothers from January 1997 to June 2002, the numbers assigned an ICD-9 code reflecting possible neonatal HSV infection

[Therapy of the acute uncomplicated urinary tract infection]. / Therapie der akuten unkomplizierten Harnweginfektion.

Acute uncomplicated cystitis and acute uncomplicated pyelonephritis are two frequently encountered urinary tract infections (UTI) in premenopausal, healthy females. Recent epidemiological investigations showed that the incidence of these infections is higher than expected. Surveys on healthcare practices in North America revealed a high variability in the therapy of uncomplicated UTI. Standardized criteria for diagnosis and therapy of uncomplicated UTIs therefore are important in order to achieve sufficient sensitivity and specificity in clinical practice. The Infectious Diseases Society of America (IDSA) developed evidence-based guidelines for the treatment of acute uncomplicated cystitis and acute uncomplicated pyelonephritis, which were recently updated by other expert groups.

[Recurrent urinary tract infection in women. Long-term antibiotic prophylaxis]. / Rezidivierende Harnwegsinfektionen der Frau. Antibiotische Langzeitprophylaxe.

Urinary tract infections (UTI) are among the most frequent bacterial infections in women. Mostly young women and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI), defined as >or=3 UTI/year. Modifiable predisposing factors are rare. The differential diagnosis between relapse and reinfection is decisive for therapy. Antibiotic prophylaxis has emerged as one of the most important therapeutic principles in rUTI. Depending on the drug utilized, the various modes of action are described as reducing the number of uropathogens in the gut and vaginal flora and/or in repeatedly eliminating bacteria from the urine. According to the European Association of Urology guidelines, nitrofurantoin, trimethoprim, and cotrimoxazole are available as first-line drugs. Cephalexin and the quinolones should be restricted to specific indications. Depending on the case, long-term antibiotic prophylaxis for 6 months, postcoital single dose prophylaxis, or patient-initiated self-start therapy can all be used successfully. Given the correct indications, the recurrence rate of rUTI can be reduced by 95%.

Maternal influenza during pregnancy and risk of congenital abnormalities in offspring.

BACKGROUND: The teratogenic effect of influenza viruses is currently being debated, and we examined the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) to study the possible association between maternal influenza and various congenital abnormalities (CAs). METHODS: The 1980-1996 HCCSCA includes 22,843 newborns or fetuses with CAs, and 38,151 matched controls (newborn infants without any abnormalities). RESULTS: In the case group, 1328 (5.8%) mothers had influenza at some time during their pregnancies compared to 1838 (4.8%) mothers in the control group (adjusted prevalence odds ratios [PORs], 1.3; 95% confidence interval [CI], 1.2-1.4). In the calculation of the adjusted PORs, the use of antifever drugs and maternal employment status were considered. When cases and their matched controls were compared, there was a higher prevalence of maternal influenza during the second and/or third month of pregnancy for the group of newborns with cleft lip +/- palate (adjusted POR, 3.2; 95% CI, 2.0-5.3), neural-tube defects (adjusted POR, 1.9; 95% CI, 1.1-3.3), and cardiovascular malformations (adjusted POR, 1.7; 95% CI, 1.3-2.3). However, a direct teratogenic effect from influenza viruses appears to be unlikely, and we suggest that the higher prevalence of the CAs indicated above can be explained mainly by fever, because this risk was reduced by the use of antifever drugs. Periconceptional folic acid supplementation also showed some preventive effect for these CAs. CONCLUSIONS: The indirect teratogenic effect of maternal influenza during pregnancy may be restricted by appropriate medical treatment (e.g., antifever drugs) and periconceptional folic acid supplementation.

Some characteristics of the HIV epidemic in Morocco.

The first case of AIDS in Morocco was declared in 1986 and since then the number of AIDS cases has steadily increased. According to the Ministry of Health, the cumulative number of AIDS cases in December 2002 was 1085. HIV in Morocco is acquired mainly through heterosexual intercourse. Individuals aged between 30 and 39 years and in the regions of Marrakech and Agadir have been the most affected. Monitoring of the trend of the epidemic by sentinel surveillance surveys indicates that Morocco is still a low prevalence zone, since prevalence among pregnant women is less than 1%. The estimated number of HIV-infected people in Morocco is around 15 000. It is not clear why the epidemic here has not evolved as it has in the sub-Saharan countries where it is spreading at an alarming rate. Late introduction of HIV-1 subtype B in Morocco, which is relatively less transmissible, circumcision and reduced risk behaviours of Muslims may explain this. Nonetheless, because prevalence has increased in recent years, unless preventive measures are strengthened, the HIV epidemic will worsen in Morocco.

Iron and its relation to immunity and infectious disease.

The continuing unresolved debate over the interaction of iron and infection indicates a need for quantitative review of clinical morbidity outcomes. Iron deficiency is associated with reversible abnormalities of immune function, but it is difficult to demonstrate the severity and relevance of these in observational studies. Iron treatment has been associated with acute exacerbations of infection, in particular, malaria. Oral iron has been associated with increased rates of clinical malaria (5 of 9 studies) and increased morbidity from other infectious disease (4 of 8 studies). In most instances, therapeutic doses of oral iron were used. No studies in malarial regions showed benefits. Knowledge of local prevalence of causes of anemia including iron deficiency, seasonal malarial endemicity, protective hemoglobinopathies and age-specific immunity is essential in planning interventions. A balance must be struck in dose of oral iron and the timing of intervention with respect to age and malaria transmission. Antimalarial intervention is important. No studies of oral iron supplementation clearly show deleterious effects in nonmalarious areas. Milk fortification reduced morbidity due to respiratory disease in two very early studies in nonmalarious regions, but this was not confirmed in three later fortification studies, and better morbidity rates could be achieved by breast-feeding alone. One study in a nonmalarious area of Indonesia showed reduced infectious outcome after oral iron supplementation of anemic schoolchildren. No systematic studies report oral iron supplementation and infectious morbidity in breast-fed infants in nonmalarious regions.

"But I know my man!" HIV/AIDS risk appraisals and heuristical reasoning patterns among childbearing women.

This exploratory study examined HIV/AIDS risk appraisals, life-style choices, and heuristical reasoning patterns reported by 105 urban childbearing women. The availability heuristic was the strategy most frequently described by participants to distance themselves from the risks of having or getting HIV/AIDS within the social and communal context of their lives. The findings suggest that objective (provider) and subjective (client) interpretations of HIV/AIDS risks should be incorporated into pragmatic prevention programs initiated by nurses. The data further suggest that such urban childbearing women must be involved in ongoing HIV/AIDS prevention and early-intervention initiatives throughout their reproductive lives.

Fatal maternal tetanus following premature rupture of membranes and retained dead fetus.

A fatal case of tetanus arising from premature rupture of membranes in a retained dead fetus is presented. The condition followed the vaginal insertion of some herbs by a local herbalist. The case illustrates the danger of anaerobic infection in the presence of intrauterine fetal death particularly when it is complicated by premature rupture of membranes. Undue vaginal manipulation as happened in this case is an additional hazard and should be avoided.

Nosocomial outbreak of Pseudomonas aeruginosa folliculitis associated with a physiotherapy pool.

Outbreaks of community-acquired Pseudomonas aeruginosa folliculitis have recently been described in association with health spa whirlpools. In February 1984 we detected an outbreak of Pseudomonas folliculitis among hospital staff and patients using a swimming pool in a newly constructed physiotherapy unit. A rash developed in 5 (45%) of the 11 physiotherapists who had used the pool, as compared with 0 of the 17 who had not (p less than 0 005). Pseudomonas folliculitis also developed in 6 (21%) of 29 outpatients and 4 (33%) of 12 inpatients who had used the facility; Pseudomonas infection of a surgical wound also developed in 1 of the 4 inpatients. The epidemic curve was consistent with a continuing common-source outbreak. P. aeruginosa, serotype O:10, was isolated from three physiotherapists, the patient with an infected surgical wound and the pool. A case-control study of pool users did not identify risk factors for infection, although the physiotherapists had spent longer in the pool than had the patients. After hyperchlorination and structural repairs to the pool, no further cases were identified among pool users. This outbreak is the first reported nosocomial outbreak of Pseudomonas folliculitis. Further investigation is needed to determine the risk of serious Pseudomonas infections in hospitalized patients using physiotherapy pools.

Effect of maternal parasitic disease on the neonate.

Parasitic disease is the most common infectious disease complication of pregnancy worldwide, resulting in maternal debilitation and fetal prematurity and low birth weight. The increasing incidence of these diseases in our population led to the present study of 125 patients, 34 of whom were found to be infected with at least one intestinal parasite. In contrast to studies in developing countries, no significant differences in either maternal anemia, or fetal birth weight, or prematurity were found between the infected and non-infected groups. However, there was a three-fold increase in the incidence of significant neonatal hyperbilirubinemia in the parasitized group. Parasitic disease complicating pregnancy in our population does not appear to exert the same adverse effect on mother and fetus as that described in other countries. In view of the limited pathology associated with parasitic disease, treatment, other than with iron and vitamin supplementation, is not routinely indicated in pregnancy in populations similar to ours. However, due to the increased incidence of neonatal jaundice and morbidity we would recommend close observation of the neonates in the immediate postpartum period.

The genesis of amniotic fluid infections.

Amniotic fluid infections manifested by an inflammatory response in the extraplacental membranes and subchorionic plate of the placenta are a common phenomenon thought to be due in most cases to ascending bacterial infections via intact membranes. Fatal spread to the fetus is much less common and more likely to occur in underprivileged communities. The probable reasons are nutritional deprivation in the mother or both, leading to production of a liquor with diminished ability to suppress bacterial growth. Zinc is one component of the antibacterial system but liquor levels of zinc vary widely and inconsistently with antibacterial activity. Dietary supplementation with zinc did not improve antibacterial activity of liquors in a population with diminished liquor antibacterial activity and large number of fatal infections. Other factors in the genesis of amniotic fluid infections may be interference with normal defence mechanisms as a result of coitus in late pregnancy and vaginal infections with Trichomonas vaginalis. Socioeconomic factors may play a role apart from their association with maternal nutrition, through diminished hygiene associated with insufficient use of water and insufficient availability and use of medical facilities.