Anti-erythrocyte immunization in the pregnant woman. Apropos of the analysis of 761 cases of alloimmunized women delivered in the Paris area in 1978 and 1979

Through analysis of 760 cases of allo-immunized women delivered in the Paris area during 1978 and 1979, anti-erythrocyte immunization (ABO excluded) still appears to be a consequent perinatal risk, for the mother as for her fetus. During the considered period, general incidence in the parisian population has been of 3,78 for 1 000 livebirths, one out of four cases being a "non Rh D"immunization. Obviously, anti-D immunoglobulin prophylaxis has not proved to be as efficient as it promised to be, after more than ten years of application. Taking into account cases affecting "non ordinary" residents in the observed area, incidence of anti-D immunizations was of two out of a thousand. Anti-D immunoglobulin actual efficiency cannot be incriminated, for when correctly applied Rhesus immunization prophylaxis has demonstrated its ability to induce a twenty-fold reduction of immunization risk due to pregnancy. It must be pointed out, unfortunately, that most cases of undue immunizations are related to prophylatic omissions after delivery, miscarriage, abortion or fortuitous hetero-Rhesus blood transfusion. On another hand an important increase of "non Rh D" immunizations, which incidence, if one images that unknown cases are as frequent as known cases, could be two out of a thousand deliveries, is perhaps able to neutralize partially the decrease of Rh D immunizations. Though is underlined the absolute necessity to extend systematically anti-erythrocyte antibody screenings to all pregnant women, whatever the blood group is. A great variety of antibodies specificities can be found among "on Rh D" immunizations but anti-Kell and anti-c are by far the most frequently met. In most cases theses immunizations could easily be avoided, assessing that all female subjects aged less than 50 years are only given Kell negative and, if lacking c antigen, CC phenotyped blood.     

Attitudes toward Infection Prophylaxis in Pediatric Oncology: A Qualitative Approach

Background

The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology.

Methods

The study was completed in three phases: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach.

Results

A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration.

Conclusion

Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.     

Obtaining anti-tetanus immunoglobulin from blood plasma of immunized dogs

Dogs were immunized by tetanic anatoxin. Eight series of antitetanic immunoglobulin with the antitoxin activity from 100.10(3) IU/l to 700.10(3) IU/l were produced from blood plasma. That immunoglobulin was used to study passive and active-passive immunization for tetanus prophylaxis and treatment in the strictly allogenic system.     

Effect of immunoglobulin prophylaxis on the incidence of the development of anicteric forms of hepatitis A

As the result of the clinico-biochemical examination of children in the foci of hepatitis A, carried out under the conditions of a strictly controlled epidemiological trial, the data on the frequency of the formation of the anicteric forms of hepatitis A in the course of the realization of different tactics of immunoglobulin prophylaxis have been established. The administration of immunoglobulin in a single injection has been shown to decrease the number of both manifest and anicteric forms of hepatitis A two times in comparison with the control. The administration of the preparation on contacts with hepatitis A patients in areas with a high morbidity level has been found to produce no decrease in the frequency of the manifest and anicteric forms of hepatitis A, this frequency remaining on the level registered in the control groups.     

Controversial and unsolved problems in the prevention of infectious hepatitis]

Data are presented indicating that 1 ml of 10% and 1% immunoglobulin possessed similar epidemiological activity in the prophylaxis of infectious hepatitis. It was shown that redical action of infectious hepatitis on the epidemic process was possible only in case of embracement by immunoglobulin vaccination of not less than 80% of children aged from 1 to 11 years. The economic effect of the introduction of 1% immunoglobulin constituted about 40 000 roubles per 100 000 persons vaccinated. Besides, a possibility of side-effects were nilin case of placental immunoglobulin since in the 1% preparation nonspecific biologically active substances could penetrate in much lesser amounts.     

Evaluation of Hepatitis A Vaccine in Post-Exposure Prophylaxis,The Netherlands, 2004-2012

Background

The secondary attack rate of hepatitis A virus (HAV) among contacts of cases is up to 50%. Historically, contacts were offered immunoglobulin (IG, a human derived blood product) as post-exposure prophylaxis (PEP). Amid safety concerns about IG, HAV vaccine is increasingly recommended instead. Public health authorities’ recommendations differ, particularly for healthy contacts ≥40 years old, where vaccine efficacy data is limited. We evaluated routine use of HAV vaccine as an alternative to immunoglobulin in PEP, in those considered at low risk of severe infection in the Netherlands.

Methods

Household contacts of acute HAV cases notified in Amsterdam (2004-2012) were invited ≤14 days post-exposure, for baseline anti-HAV testing and PEP according to national guidelines: immunoglobulin if at risk of severe infection, or hepatitis A vaccine if healthy and at low risk (aged <30, or, 30-50 years and vaccinated <8 days post-exposure). Incidence of laboratory confirmed secondary infection in susceptible contacts was assessed 4-8 weeks post-exposure. In a vaccinated subgroup, relative risk (RR) of secondary infection with estimated using Poisson regression.

Results

Of 547 contacts identified, 191 were susceptible to HAV. Per-protocol, 167 (87%) were vaccinated (mean:6.7 days post-exposure, standard deviation(sd)=3.3) and 24 (13%) were given immunoglobulin (mean:9.7 days post-exposure, sd=2.8). At follow-up testing, 8/112 (7%) had a laboratory confirmed infection of whom 7 were symptomatic. All secondary infections occurred in vaccinated contacts, and half were >40 years of age. In healthy contacts vaccinated per-protocol ≤8 days post-exposure, RR_{ref. ≤15 years} of secondary infection in those >40 years was 12.0 (95%CI:1.3-106.7).

Conclusions

Timely administration of HAV vaccine in PEP was feasible and the secondary attack rate was low in those <40 years. Internationally, upper age-limits for post-exposure vaccination vary. Pending larger studies, immunoglobulin should be considered PEP of choice in people >40 years of age and those vulnerable to severe disease.     

Prophylaxis against hepatitis A for travel.

OBJECTIVE--To develop a rational practice policy for prophylaxis against hepatitis A for travellers to high risk areas. DESIGN--18 Month prospective study of consecutive patients who requested prophylaxis against hepatitis A. SETTING--Inner city general practice. SUBJECTS--104 Patients aged 15-61 (mean 30) assessed for risk factors for hepatitis A and put into groups depending on predictions from the risk factors of their immunity. MAIN OUTCOME MEASURES AND RESULTS--All patients were screened for antibody to hepatitis A virus. Of 52 patients with no risk factors 47 had no antibody and were thus susceptible to hepatitis A. All 27 patients with major risk factors (having been brought up in an endemic area or with a history of jaundice) were immune. Of 25 patients with minor risk factors (a history of previous travel in high risk areas, drug abuse, having lived in a squat or travelled rough, or having lived with someone who had jaundice) 12 were immune (p less than 0.001, chi 2 test). CONCLUSIONS--All travellers requesting prophylaxis against hepatitis A should be assessed for risk factors for previous exposure to hepatitis A. Those with no risk factors could be immunised with human normal immunoglobulin without screening. The remainder should be tested for hepatitis A antibody and those found to be susceptible should be immunised.     

Passive immunization for the treatment and prevention of HIV infection.

Passive immunization using serum or immunoglobulin preparations has been used in the prophylaxis and treatment of many bacterial and viral diseases. Preliminary attempts to use these methods to prevent HIV infection in chimpanzees have been promising. With the identification of polyclonal and monoclonal antibodies with protective activity against HIV in in vitro systems, the possibility of using these reagents in vivo takes on new relevance. The potential and problems of using passively administered anti-HIV antibodies for HIV prophylaxis and treatment are discussed, as well as the relative merits of polyclonal versus monoclonal reagents.     

Cost-Effectiveness of Cranberries vs Antibiotics to Prevent Urinary Tract Infections in Premenopausal Women: A Randomized Clinical Trial

Background

Urinary tract infections (UTIs) are common and result in an enormous economic burden. The increasing prevalence of antibiotic-resistant microorganisms has stimulated interest in non-antibiotic agents to prevent UTIs.

Objective

To evaluate the cost-effectiveness of cranberry prophylaxis compared to antibiotic prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) over a 12 month period in premenopausal women with recurrent UTIs.

Materials and Methods

An economic evaluation was performed alongside a randomized trial. Primary outcome was the number of UTIs during 12 months. Secondary outcomes included satisfaction and quality of life. Healthcare utilization was measured using questionnaires. Missing data were imputed using multiple imputation. Bootstrapping was used to evaluate the cost-effectiveness of the treatments.

Results

Cranberry prophylaxis was less effective than TMP-SMX prophylaxis, but the differences in clinical outcomes were not statistically significant. Costs after 12 months in the cranberry group were statistically significantly higher than in the TMP-SMX group (mean difference €249, 95% confidence interval 70 to 516). Cost-effectiveness planes and cost-effectiveness acceptability curves showed that cranberry prophylaxis to prevent UTIs is less effective and more expensive than (dominated by) TMP-SMX prophylaxis.

Conclusion

In premenopausal women with recurrent UTIs, cranberry prophylaxis is not cost-effective compared to TMP-SMX prophylaxis. However, it was not possible to take into account costs attributed to increased antibiotic resistance within the framework of this randomized trial; modeling studies are recommended to investigate these costs. Moreover, although we based the dosage of cranberry extract on available evidence, this may not be the optimal dosage. Results may change when this optimal dosage is identified.

Trial Registration

ISRCTN.org ISRCTN50717094     

Safety and Efficacy of Co-Trimoxazole for Treatment and Prevention of Plasmodium falciparum Malaria: A Systematic Review

Introduction

Cotrimoxazole (CTX) has been used for half a century. It is inexpensive hence the reason for its almost universal availability and wide clinical spectrum of use. In the last decade, CTX was used for prophylaxis of opportunistic infections in HIV infected people. It also had an impact on the malaria risk in this specific group.

Objective

We performed a systematic review to explore the efficacy and safety of CTX used for P.falciparum malaria treatment and prophylaxis.

Result

CTX is safe and efficacious against malaria. Up to 75% of the safety concerns relate to skin reactions and this increases in HIV/AIDs patients. In different study areas, in HIV negative individuals, CTX used as malaria treatment cleared 56%–97% of the malaria infections, reduced fever and improved anaemia. CTX prophylaxis reduces the incidence of clinical malaria in HIV-1 infected individuals from 46%–97%. In HIV negative non pregnant participants, CTX prophylaxis had 39.5%–99.5% protective efficacy against clinical malaria. The lowest figures were observed in zones of high sulfadoxine-pyrimethamine resistance. There were no data reported on CTX prophylaxis in HIV negative pregnant women.

Conclusion

CTX is safe and still efficacious for the treatment of P.falciparum malaria in non-pregnant adults and children irrespective of HIV status and antifolate resistance profiles. There is need to explore its effect in pregnant women, irrespective of HIV status. CTX prophylaxis in HIV infected individuals protects against malaria and CTX may have a role for malaria prophylaxis in specific HIV negative target groups.     

Immunotherapy against antibiotic-resistant bacteria: the Russian experience with an antistaphylococcal hyperimmune plasmaand immunoglobulin

The Russian experience with the preparation and clinical application of an antitoxic antistaphylococcal hyperimmune plasma and immunoglobulin is described. The immunotherapies were developed in the late 1960s and put into widespread use in the Soviet Union for the prophylaxis and treatment of sepsis, pneumonia, and other conditions caused by an epidemic of antibiotic-resistant Staphylococcus aureus.     

A trial of using immunoglobulins of known specificity for preventing hepatitis A in regions with high epidemic activity

The economic effectiveness of immunoglobulin prophylaxis (IGP), carried out among children aged 1-3 at the beginning of a seasonal rise in hepatitis A (HA) morbidity with high coefficients of protection (80-85%), was directly related to the activity of the epidemic process. Preparations with sufficiently high content of antibodies to HA virus sharply decreased the manifestation of this infection. The detection rate of the manifest forms of the infection among children covered by prophylactic measures in the foci of HA was considerably lower than among children who had not received the preparation. IGP exerted no essential influence on the dynamics of the formation of population immunity. A high share of children aged 3-4 years, seropositive to HA virus (up to 90%), validates the inadvisability of carrying out IGP in older groups of children.     

Rh immunization in Manitoba: progress in prevention and management.

For two decades the perinatal mortality caused by erythroblastosis has been decreasing in Manitoba. The improved management of Rh-immunized pregnancies has lowered the death rate among affected infants from 10.8% to 3.4%, while the prevention of Rh immunization has reduced its incidence from 9.1 to 2.2 per 1000 total births. In its first 6 years and 8 months Manitoba''s antenatal prophylaxis program, in which immunoglobulin is administered to Rh-negative women at 28 weeks'' gestation, reduced the incidence of Rh immunization during pregnancy by 93%. In combination with post-abortion and postpartum prophylaxis the antenatal treatment has provided a protection rate of 98.6% among primigravidas at risk. Further improvements are expected.     

Prevention of tetanus in the wounded.

Recommendations for the prevention of tetanus in the wounded have been revised to incorporate the use of human tetanus immunoglobulin, which is now available in the United Kingdom. Surgical toilet is of prime importance for all wounds, and is usually sufficient for tetanus prophylaxis in patients with wounds that are less than six hours old, clean, non-penetrating, and with negligible tissue damage. Human tetanus immunoglobulin should be given to patients with more serious wounds sho have had toxoid injections over 10 years earlier, had an incomplete course, or do not know their immunity status. The importance of active immunization is emphasized. The recommendations should be regarded as guidelines as the circumstances in individual cases will differ.     

Prophylaxis and therapy with human immunoglobulins

The supply of human immunoglobulin preparations (Ig) is steadily increasing. On the one hand, the wide range of specificities of the so-called hyper-Ig is broadening, on the other hand, the structural variety of Ig contained in the preparations and their fragments is increasing (intact IgG, Fab, F(ab')2 fragments, desaggregation, inactivation of the complement binding site). Specificity and structure of Ig are important for the efficacy, kind of application, amount and intervals of dosage and for compatibility. Therefore, an exact knowledge of the preparation becomes more and more necessary for reasonably applying it. The development of modern IgG preparations with intravenous compatibility and intact Fc-part providing the possibility for the application of a high dosage require "old" indications to be re-examined by clinically controlled investigations, thus opening new ways to an improved efficacy in applying Ig in the prophylaxis and therapy of infections as well as to new areas of indication by recognising the immunomodulatory effects, e.g. autoimmunopathies.     

Epidemiology,Impact and Control of Rabies in Nepal: A Systematic Review

Background

Rabies is a vaccine-preventable viral zoonosis belonging to the group of neglected tropical diseases. Exposure to a rabid animal may result in a fatal acute encephalitis if effective post-exposure prophylaxis is not provided. Rabies occurs worldwide, but its burden is disproportionately high in developing countries, including Nepal. We aimed to summarize current knowledge on the epidemiology, impact and control of rabies in Nepal.

Methods

We performed a systematic review of international and national scientific literature and searched grey literature through the World Health Organization Digital Library and the library of the National Zoonoses and Food Hygiene Research Centre, Nepal, and through searching Google and Google Scholar. Further data on animal and human rabies were obtained from the relevant Nepalese government agencies. Finally, we surveyed the archives of a Nepalese daily to obtain qualitative information on rabies in Nepal.

Findings

So far, only little original research has been conducted on the epidemiology and impact of rabies in Nepal. Per year, rabies is reported to kill about 100 livestock and 10–100 humans, while about 1,000 livestock and 35,000 humans are reported to receive rabies post-exposure prophylaxis. However, these estimates are very likely to be serious underestimations of the true rabies burden. Significant progress has been made in the production of cell culture-based anti-rabies vaccine and rabies immunoglobulin, but availability and supply remain a matter of concern, especially in remote areas. Different state and non-state actors have initiated rabies control activities over the years, but efforts typically remained focalized, of short duration and not harmonized. Communication and coordination between veterinary and human health authorities is limited at present, further complicating rabies control in Nepal. Important research gaps include the reporting biases for both human and animal rabies, the ecology of stray dog populations and the true contribution of the sylvatic cycle.

Interpretation

Better data are needed to unravel the true burden of animal and human rabies. More collaboration, both within the country and within the region, is needed to control rabies. To achieve these goals, high level political commitment is essential. We therefore propose to make rabies the model zoonosis for successful control in Nepal.     

Pre- and postexposure protection by passive immunoglobulin but no enhancement of infection with a flavivirus in a mouse model.

Antibody-dependent enhancement of flavivirus infection, which except for dengue virus is without clear proof in vivo, is still under debate. Recently, postexposure immunoglobulin prophylaxis against tick-borne encephalitis virus, a flavivirus, was claimed to possibly have worsened the outcome of infection due to antibody-dependent enhancement. In the present study, antibody-dependent enhancement and pre- or postexposure protection by passive administration of tick-borne encephalitis virus immunoglobulin were evaluated in a mouse model. Preexposure treatment with homologous murine or heterologous human immunoglobulin provided complete protection against lethal challenge with tick-borne encephalitis virus. For postexposure treatment with antibody, the degree of protection correlated with the amount of immunoglobulin administered and was inversely related to the time interval between infection and treatment. Indications of enhancement of infection would have been increased lethality or reduced mean survival time, but neither was observed under the conditions used in our experiments despite the broad range of immunoglobulin and virus challenge doses applied. In contrast to these in vivo results, antibody-dependent enhancement of tick-borne encephalitis virus infection of murine peritoneal macrophages was readily demonstrable in vitro. Thus, antibody-dependent enhancement of viral infection in vitro does not necessarily predict enhancement in vivo.     

Is travel prophylaxis worth while? Economic appraisal of prophylactic measures against malaria,hepatitis A,and typhoid in travellers.

OBJECTIVES--To estimate the costs and benefits of prophylaxis against travel acquired malaria, typhoid fever, and hepatitis A in United Kingdom residents during 1991. DESIGN--Retrospective analysis of national epidemiological and economic data. MAIN OUTCOME MEASURES--Incidence of travel associated infections in susceptible United Kingdom residents per visit; costs of prophylaxis provision from historical data; benefits to the health sector, community, and individuals in terms of avoided morbidity and mortality based on hospital and community costs of disease. RESULTS--The high incidence of imported malaria (0.70%) and the low costs of providing chemoprophylaxis resulted in a cost-benefit ratio of 0.19 for chloroquine and proguanil and 0.57 for a regimen containing mefloquine. Hepatitis A infection occurred in 0.05% of visits and the cost of prophylaxis invariably exceeded the benefits for immunoglobulin (cost-benefit ratio 5.8) and inactivated hepatitis A vaccine (cost-benefit ratio 15.8). Similarly, low incidence of typhoid (0.02%) and its high cost gave whole cell killed, polysaccharide Vi, and oral Ty 21a typhoid vaccines cost-benefit ratios of 18.1, 18.0, and 22.0 respectively. CONCLUSIONS--Fewer than one third of travellers receive vaccines but the total cost of providing typhoid and hepatitis A prophylaxis of 25.8m pounds is significantly higher than the treatment costs to the NHS (1.03m pounds) of cases avoided by prophylaxis. Neither hepatitis A prophylaxis nor typhoid prophylaxis is cost effective, but costs of treating malaria greatly exceed costs of chemoprophylaxis, which is therefore highly cost effective.     

Changing Use of Surgical Antibiotic Prophylaxis in Thika Hospital,Kenya: A Quality Improvement Intervention with an Interrupted Time Series Design

Introduction

In low-income countries, Surgical Site Infection (SSI) is a common form of hospital-acquired infection. Antibiotic prophylaxis is an effective method of preventing these infections, if given immediately before the start of surgery. Although several studies in Africa have compared pre-operative versus post-operative prophylaxis, there are no studies describing the implementation of policies to improve prescribing of surgical antibiotic prophylaxis in African hospitals.

Methods

We conducted SSI surveillance at a typical Government hospital in Kenya over a 16 month period between August 2010 and December 2011, using standard definitions of SSI and the extent of contamination of surgical wounds. As an intervention, we developed a hospital policy that advised pre-operative antibiotic prophylaxis and discouraged extended post-operative antibiotics use. We measured process, outcome and balancing effects of this intervention in using an interrupted time series design.

Results

From a starting point of near-exclusive post-operative antibiotic use, after policy introduction in February 2011 there was rapid adoption of the use of pre-operative antibiotic prophylaxis (60% of operations at 1 week; 98% at 6 weeks) and a substantial decrease in the use of post-operative antibiotics (40% of operations at 1 week; 10% at 6 weeks) in Clean and Clean-Contaminated surgery. There was no immediate step-change in risk of SSI, but overall, there appeared to be a moderate reduction in the risk of superficial SSI across all levels of wound contamination. There were marked reductions in the costs associated with antibiotic use, the number of intravenous injections performed and nursing time spent administering these.

Conclusion

Implementation of a locally developed policy regarding surgical antibiotic prophylaxis is an achievable quality improvement target for hospitals in low-income countries, and can lead to substantial benefits for individual patients and the institution.     

A Survey of the Knowledge of Venous Thromboembolism Prophylaxis among the Medical Staff of Intensive Care Units in North China

Background

Guideline concordance for venous thromboembolism (VTE) prophylaxis in critically ill patients in intensive care units (ICUs) varies across different countries.

Objective

To explore how the medical staff of ICUs in China comprehend and practice VTE prophylaxis.

Method

Questionnaires comprising 39 questions and including 4 dimensions of thromboprophylaxis were administered in ICUs in North China.

Results

In all, 52 ICUs at 23 tertiary hospitals in 7 Chinese provinces and municipalities were surveyed. A total of 2500 questionnaires were sent, and 1861 were returned, corresponding to a response rate of approximately 74.4%. Of all surveyed medical staff, 36.5% of physicians and 22.2% of nurses were aware of the guidelines in China, and 19.0% of physicians and 9.5% of nurses comprehended the 9^th edition of the guidelines of the American College of Chest Physicians (ACCP). Additionally, 37.6% of the medical staff chose a prophylaxis method based on the related guidelines, and 10.3% could demonstrate the exact indication for mechanical pattern application. Worries about skin injury, difficulty with removal and discomfort during mechanical thromboprophylaxis were cited by more than 30% of nurses, which was significantly more frequent than for physicians (graduated compression stockings: 54.3% VS 34.1%, 60.7% VS 49%, and 59.4% VS 54%, p = 0.000; intermittent pneumatic compression: 31% VS 22.2%, 19.2% VS 13.9%, and 37.8% VS 27.2%, p = 0.000).

Conclusions and Relevance

The knowledge of VTE prophylaxis among the medical staff of ICUs in North China remains limited, which may lead to a lack of standardization of VTE prophylaxis. Strengthened, standardized training may help medical staff to improve their comprehension of the relevant guidelines and may finally reduce the occurrence of VTE in ICUs and improve the prognosis of critically ill patients with VTE.