Tetanus antibody titers and duration of immunity to clinical tetanus infections in free-ranging rhesus monkeys (Macaca mulatta)

Prior to 1985 tetanus was a major cause of mortality in the free-ranging colony of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual deaths. In 1985 and 1986 all animals (except infants) received primary and booster doses, respectively, of tetanus toxoid. In subsequent years primary immunizations were given to all yearlings, and boosters were administered to all 2-year-old animals during the annual capture of the colony. The main objectives of the tetanus immunization program were to reduce the pain and suffering caused by tetanus infections and to decrease mortality in the colony. Other objectives were to evaluate the efficacy of the two-dose tetanus toxoid immunization protocol and to determine whether additional boosters might be required to provide adequate long-term protection against tetanus infections. The immediate effect of the mass immunization program was the elimination of clinical tetanus infections in the population and a 42.2% reduction in the overall mortality rate. Since the immunization program began, no cases of tetanus have been observed in the colony, except in two unimmunized infants, and it has not been necessary to give tertiary injections of tetanus toxoid to maintain protection against infection. A sample collected in 2004 of the original cohort of monkeys immunized in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers (>0.01 IU/ml) at the ages of 20-23 years, which is close to the life expectancy of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid provided long-term, if not lifelong, protection against tetanus for rhesus monkeys living in a tropical clime where tetanus is enzootic and the risk of infection is great.     

Expanded program on immunization and its implementation in the Czech Socialist Republic

National immunization programs carried out in the CSR are here confronted with the EPI regional targets for Europe, a component of the WHO global program "Health for all by the year 2000". The EPI target diseases to be brought under control in Europe by 1990 include measles, poliomyelitis, diphtheria and neonatal tetanus; control of congenital rubella infection is to be achieved by the year 2000. The presented data show that Czechoslovakia has succeeded in implementing this program much ahead of the WHO time schedule. The elimination of measles infection was achieved in 1982, poliomyelitis was brought under control in 1961, and the effective diphtheria control has been in effect since the mid-1960s. Cases of neonatal tetanus are absent in the CSR since 1965, the annual incidence of postnatal tetanus is permanently 0.1-0.2 per 100,000 population. The goal of achieving the rubella-free status and thus the elimination of congenital rubella cases at country level is expected to be reached in the early 1990s. Implementation of the remaining WHO recommendations pertinent to infections other than EPI target diseases appears also satisfactory. Regular immunization against whooping cough, one of the oldest immunization programs in Czechoslovakia, succeeded in effectively eliminating this infection in the early 1970s. Selective immunization campaigns against influenza infection, introduced many years ago, help protect, together with a large-scale use of available chemoprophylactics, some 200,000 individuals every year in CSR. The hepatitis B immunization program was started in 1983 and is primarily limited to health service staff, which is in line with the existing WHO recommendations. Inception of the regular immunization program against mumps is planned for the beginning of 1987.     

The control of viral diseases in the developing countries with the use of existing vaccines]

In developing countries, every year about 70 million measles cases occur with 1.5 million deaths, over 200,000 children contract paralytic poliomyelitis, 50 million people get infected with viral B hepatitis causing over 1 million deaths, and several thousand people perish because of yellow fever according to WHO data. At the present time, there are 12 vaccines against viruses: vaccines against German measles and mumps in addition to the above. The universal immunization program (UIP) of WHO targets measles and polio. In 1989, a WHO resolution envisioned a 90% immunization coverage by the year 2000. Measles vaccination is recommended for children aged 9-23 months, since most children have maternal antibodies during the first 3-13 months of age. The Edmonston-Zagreb vaccine provided seroconversion of 92, 96, and 98% for 18 months vs. the 66, 76, and 91% rate of the Schwarz vaccine. In the US, measles incidence increased from 1497 cases in 1983 to 6382 cases in 1988 to over 14,000 cases in 1989, prompting second vaccination in children of school age. The highest incidence of polio was registered in Southeast Asia, although it declined from 1 case/100,000 population in 1975 to .5/100,000 in 1988. Oral poliomyelitis vaccine (OPV) provides protection: there is only 1 case/2.5 million vaccinations. Hepatitis B has infected over 2 billion people. About 300 million are carriers, with a prevalence of 20% in African, Asian, and Pacific region populations. Plasmatic and bioengineered recombinant vaccine type have been used in 30 million people. The first dose is given postnatally, the second at 1-2 months of age, and the 3rd at 1 year of age. Yellow fever vaccine was 50 years old in 1988, yet during 1986-1988 there were 5395 cases with 3172 deaths in Africa and South America. Vaccination provides 90-95% seroconversion, and periodic follow-up vaccinations under UIP could eradicate these infections and their etiologic agents.     

Improving Outcomes in Infants of HIV-Infected Women in a Developing Country Setting

Background

Since 1999 GHESKIO, a large voluntary counseling and HIV testing center in Port-au-Prince, Haiti, has had an ongoing collaboration with the Haitian Ministry of Health to reduce the rate of mother to child HIV transmission. There are limited data on the ability to administer complex regimens for reducing mother to child transmission and on risk factors for continued transmission and infant mortality within programmatic settings in developing countries.

Methods and Findings

We analyzed data from 551 infants born to HIV-infected mothers seen at GHESKIO, between 1999 and 2005. HIV-infected mothers and their infants were given “short-course” monotherapy with antiretrovirals for prophylaxis; and, since 2003, highly active antiretroviral therapy (HAART) when clinical or laboratory indications were met. Infected women seen in the pre-treatment era had 27% transmission rates, falling to 10% in this cohort of 551 infants, and to only 1.9% in infants of women on HAART. Mortality rate after HAART introduction (0.12 per year of follow-up [0.08–0.16]) was significantly lower than the period before the availability of such therapy (0.23 [0.16–0.30], P<0.0001). The effects of maternal health, infant feeding, completeness of prophylaxis, and birth weight on mortality and transmission were determined using univariate and multivariate analysis. Infant HIV-1 infection and low birth weight were associated with infant mortality in less than 15 month olds in multivariate analysis.

Conclusions

Our findings demonstrate success in prevention of mother-to-child HIV transmission and mortality in a highly resource constrained setting. Elements contributing to programmatic success include provision of HAART in the context of a comprehensive program with pre and postnatal care for both mother and infant.     

Manufacturing and supply of monovalent oral polio vaccines.

A new polio vaccine was developed, produced and licensed by sanofi pasteur at the request of the World Health Organization (WHO) for mass immunization campaigns in endemic countries such as Egypt. The new vaccine, monovalent oral polio vaccine 1 or mOPV1, is currently used in Egypt as a critical part of a new WHO strategy to end polio type 1 transmission by the end of the year 2005 (types 2 and 3 polioviruses have already been eliminated from Egypt). To answer this specific need, an urgent program was mounted by Sanofi pasteur to manufacture 50million doses for Egypt, in close collaboration with WHO and National Regulatory Agencies (France and Egypt). The joint efforts between manufacturer, regulators and the WHO resulted in the quickest ever vaccine development and licensure and WHO pre-qualification. The production of mOPV was based on existing tOPV but with appropriate "change control" procedures to assure the quality of the product, and to distinguish mOPV from tOPV. Key success factors included clear and careful definition of the project; close collaboration between manufacturer, regulators and WHO; and commitment and motivation of staff. As a result, development and production of mOPV1 vaccine were carried out in a drastically reduced time period, leading to the release and delivery of the first 15 million doses of mOPV1 in April 2005.     

Vaccine preventable viral diseases in developing countries

There are several viral infectious diseases with a high impact on developing countries which can be prevented by immunization with existing vaccines. The most important are poliomyelitis, measles, hepatitis B and yellow fever. Vaccines against poliomyelitis and measles used within the framework of the WHO/Expanded Programme on Immunization prevent about 1.4 million deaths from measles and 360,000 cases of paralytic polio per year in developing countries, but about 1.5 million measles' deaths and 200,000 cases of paralytic polio still occur. Hepatitis B infection and its sequelae are responsible for over 50 million infections and one million deaths annually. Highly effective hepatitis B vaccines are now available and the price of these vaccines for the developing world has fallen dramatically. Despite the availability of a safe and efficacious yellow fever vaccine since 1937, 5400 cases of this disease with 3200 deaths were reported in Africa and South America from 1986 to 1988. Because of the efficacy of existing vaccines and the lack of animal reservoirs or vectors, systematic vaccination programmes within the framework of the Expanded Programme on Immunization (EPI) could theoretically eliminate and even eradicate poliomyelltis, measles and hepatitis B. Many different obstacles need to be overcome before these goals are realized.This paper was presented at the IUMS Symposium on New Developments in Diagnosis and Control of Infectious Diseases held in conjunction with the Eighth International Congress of Virology, Berlin, Germany, 24–31 August 1990.     

Change in immunisation schedule and sudden infant death syndrome in Hungary

Infant mortality in Hungary was higher than in other European countries; however, the reported incidence of sudden infant death syndrome (SIDS) has been lower than those for Western Europe and the United States. Childhood immunisation has been reported to be a protective factor for SIDS. In Britain, the change to an earlier immunisation schedule for diphtheria, pertussis, and tetanus appeared to be associated with a shift in the age distribution of SIDS. In 1999, immunisation for Haemophilus influenzae type b (Hib) was introduced for Hungarian infants at the age of 2 months. Data for total infant mortality and SIDS in Hungary were analysed between 1990 and 2002. Infection was the major cause of death among Hungarian infants followed by SIDS. Following introduction of Hib immunisation, there was a decrease in deaths due to meningitis from an average of 3.5% of all infant deaths between 1990 and 1998 to an average of 1% of all infant deaths between 1999 and 2002 (p=0.00). There was also a significant decrease in the proportion of SIDS in the age range > or =2 months from 48% in the earlier period to 39% after introduction of the vaccine (p=0.03). The decrease in SIDS might be due in part to decrease in unrecognised Hib infections or to induction of antibodies by the tetanus toxoid to which the Hib polysaccharide is conjugated that are cross reactive with bacterial toxins implicated in SIDS.     

Implications of armed conflict for maternal and child health: A regression analysis of data from 181 countries for 2000–2019

BackgroundArmed conflicts have major indirect health impacts in addition to the direct harms from violence. They create enduring political instability, destabilise health systems, and foster negative socioeconomic and environmental conditions—all of which constrain efforts to reduce maternal and child mortality. The detrimental impacts of conflict on global maternal and child health are not robustly quantified. This study assesses the association between conflict and maternal and child health globally.Methods and findingsData for 181 countries (2000–2019) from the Uppsala Conflict Data Program and World Bank were analysed using panel regression models. Primary outcomes were maternal, under-5, infant, and neonatal mortality rates. Secondary outcomes were delivery by a skilled birth attendant and diphtheria, pertussis, and tetanus (DPT) and measles vaccination coverage. Models were adjusted for 10 confounders, country and year fixed effects, and conflict lagged by 1 year. Further lagged associations up to 10 years post-conflict were tested. The number of excess deaths due to conflict was estimated. Out of 3,718 country–year observations, 522 (14.0%) had minor conflicts and 148 (4.0%) had wars. In adjusted models, conflicts classified as wars were associated with an increase in maternal mortality of 36.9 maternal deaths per 100,000 live births (95% CI 1.9–72.0; 0.3 million excess deaths [95% CI 0.2 million–0.4 million] over the study period), an increase in infant mortality of 2.8 per 1,000 live births (95% CI 0.1–5.5; 2.0 million excess deaths [95% CI 1.6 million–2.5 million]), a decrease in DPT vaccination coverage of 4.9% (95% CI 1.5%–8.3%), and a decrease in measles vaccination coverage of 7.3% (95% CI 2.7%–11.8%). The long-term impacts of war were demonstrated by associated increases in maternal mortality observed for up to 7 years, in under-5 mortality for 3–5 years, in infant mortality for up to 8 years, in DPT vaccination coverage for up to 3 years, and in measles vaccination coverage for up to 2 years. No evidence of association between armed conflict and neonatal mortality or delivery by a skilled birth attendant was found. Study limitations include the ecological study design, which may mask sub-national variation in conflict intensity, and the quality of the underlying data.ConclusionsOur analysis indicates that armed conflict is associated with substantial and persistent excess maternal and child deaths globally, and with reductions in key measures that indicate reduced availability of organised healthcare. These findings highlight the importance of protecting women and children from the indirect harms of conflict, including those relating to health system deterioration and worsening socioeconomic conditions.

Mohammed Jawad and co-workers report on a global analysis of maternal and child health outcomes in situations of armed conflict.     

The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

Background

Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts.

Methods and Findings

We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses.

Conclusions

Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be tailored to countries using local epidemiologic and programmatic data.     

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.     

The cluster method in conducting epidemiological research

The Expanded Programme on Immunization (EPI) whose goal is to reduce morbidity and mortality by providing children with immunizations against diphtheria, pertussis, tetanus, poliomyelitis, measles, and tuberculosis continually faces the problem of documenting immunization coverage rates. Therefore the EPI seeks simple, effective, and inexpensive methods of evaluation which could be implemented in different countries. An example of such a method is a simplified cluster sampling technique of estimation of immunization coverage through the examination of 210 children, selected randomly as 30 groups of 7 children each. In 1978-1984 more than 1000 immunization coverage surveys were performed all over the world, mainly in developing countries. In a modified way this method is also used to collect data on morbidity and mortality of certain EPI target diseases as well as diarrhoeal diseases.     

Breast-feeding pattern in an urban Nigerian community

This paper examines the pattern of breastfeeding among women still in their prime childbearing ages (15-35 years) in Ilorin, the capital city of Kwara state in Nigeria. While breastfeeding is still a common practice among urban women, there is wide variation in the duration of breastfeeding depending on the socioeconomic characteristics of the mothers. Mother's education and father's education have very strong negative associations with duration of breastfeeding. Use of contraception also has a significant independent but negative effect on breastfeeding duration. Christians continue breastfeeding for shorter periods than Muslims. The introduction of supplementary feedings to the infant occurs in this population much earlier than is recommended by various authorities. Decline in breastfeeding practice may have deleterious effects on the health and survival of children in developing countries and may also lead to higher fertility and more rapid population growth. The high morbidity and mortality among artificially fed infants in many developing countries can be attributed to improper preparation as well as contamination of infant formula and other foods.     

Helicobacter pylori vaccine development and use: a cost-effectiveness analysis using the Institute of Medicine Methodology

Background. Prophylactic vaccination has been suggested as a better strategy than antibiotics to control Helicobacter pylori infection. We evaluated the cost-effectiveness (CE) of H. pylori vaccine development and use in the United States and developing countries, using a method developed by the Institute of Medicine (IOM).
Methods. The IOM model includes costs of vaccine development, vaccination program, and averted medical treatments; morbidity and mortality prevented; expected efficacy and use; and proportion of disease that is vaccine-preventable. The model employs infant mortality equivalence (IME) to estimate disease burden; with IME, the societal cost of infection-related morbidity is expressed as equivalent to a specific rate of infant deaths. We tested model assumptions by univariate sensitivity analyses.
Results. In the United States, H. pylori vaccine would save 1,176 IME and would cost $58.71 million (1997 dollars) annually, yielding a CE ratio of $49,932 per IME; the health benefits would exceed all IOM-studied vaccines, even when efficacy dropped to 55%. H. pylori vaccine could be cost-saving if priced at less than $60 per course. In developing countries, H. pylori vaccine would rank unfavorably both in terms of health benefits (33,518 IME) and costs ($5,254 million). None of the changes in assumptions improved significantly the H. pylori vaccine's ranking relative to other IOM-studied vaccines.
Conclusions. Compared to other vaccines evaluated in the IOM study, H. pylori vaccine warrants public resource allocation for accelerated development and use in the United States but not for use in developing countries.     

African heads of state promise action against malaria

Heads of state of Africa signed a pledge to reduce the continent's malaria mortality by 50% by 2110 at an international summit of Malaria in Abuja, Nigeria. The primary focus of the malaria control program will be insecticide-treated bednets. The WHO wants a 30-fold increase in the availability of bednets in the next 5 years, as well as immediate access to cheap and effective antimalarial combination therapy for families at risk of malaria, including pregnant women. Malaria control requires annual donations of US$1 billion from industrialized countries. However, donations alone will be insufficient unless there is immediate debt cancellation, says Jeffrey Sachs, director of the Center for International Development at Harvard. The World Bank also raised criticisms concerning the US$150 million annual donation. In response, Ok Pannenborg of the World Bank stated that there are 100 World Bank operations all over Africa and its US$150 million annual donation for African malarial control projects is money they can use, but whether they use it is another matter.     

Maternal cocaine use and genitourinary tract malformations

A specific fetal disruption syndrome associated with maternal cocaine use has not as yet been documented. In the first 23 pregnancies evaluated in our program for chemically dependent women, one infant with prune belly syndrome and one infant with hypospadias were delivered to cocaine-using women. In the present study, all infants delivered in our program received a renal ultrasound at 2-3 days of life. Fifty infants born to cocaine-using women (group I) and 30 born to polydrug, noncocaine-using women (group II) were evaluated. The two groups of women were similar for age, gravidity, and race. Mean birth weight of the infants in the two groups was similar. Seven infants in group I demonstrated genitourinary tract malformations while there were no infants with such malformations in group II. It is hypothesized that the vasoconstrictive effects of cocaine could explain the abnormalities of the genitourinary tract found in the cocaine-exposed infants.     

Experience of the People's Republic of Bulgaria in controlling diphtheria, tetanus and whooping cough

The analysis of the morbidity and mortality rates in diphtheria, tetanus and pertussis in Bulgaria after the introduction of the compulsory mass immunization of children with combined DPT vaccine is presented. These data indicate that morbidity in diphtheria, tetanus and pertussis has sharply decreased. Favorable results with respect to these three diseases are the consequence of the complete coverage of the child population by immunization with the vaccine whose quality has been steadily improving for the last 20 years. A higher purity of toxoids has been achieved, and at present it exceeds the latest WHO requirements. Pertussis vaccine is produced with the use of strains whose serological characteristics correspond to those of the pertussis strains circulating in the country. The study of the reactogenicity of DPT vaccine, carried out over the period of 20 years, has shown that the vaccine has low reactogenicity.     

Doing something about tuberculosis

The phenomenal success public health officials enjoyed in controlling tuberculosis (TB) in developed countries has not been mirrored in developing countries, where TB still accounts for 25% of preventable deaths in adults. The fact that there are 8 million new cases each year (95% in developing countries) and 3 million deaths (98% in developing countries) led to the 1993 declaration by the World Health Organization (WHO) that TB poses a global emergency. Because TB is predominantly a disease of impoverished people, indifference has led to the fallacious and naive view that eradication of TB simply requires socioeconomic development. In response to this indifference, the WHO is promoting a "Stop TB--Use DOTS" campaign. DOTS, a strategy based on directly observed therapy, also requires government commitment, a regular supply of drugs, effective diagnoses, and an audit of the efficacy of the strategy. While the treatment of TB is among the most cost-effective of all medical interventions in terms of years of healthy life saved, the DOTS campaign requires a considerable dedication of funds. Renewed interest in TB is leading the US and the UK to increase support for control programs. In addition, a new UK-based charity, "TB Alert," hopes to play a major role in advocating for political commitment to and funding for TB control.     

Concern mounts over female genital mutilation

According to estimates by the WHO, up to 140 million girls and women have undergone female genital mutilation (FGM), and each year another 2 million are thought to be at risk of it. Most girls who undergo this ritual live in Africa and to a lesser extent in Asia and the Middle East. However, there has been an increasing occurrence of genital mutilations among migrants from these countries who have settled in the US, Europe, and Australia. Although some countries prohibit the practice, evidence suggests that these laws are defied. In the UK, Baroness Ruth Rendell, the prime mover behind a cross-party parliament inquiry into FGM is convinced that some health professionals are still carrying out the operation on request. To this effect, she is advocating some prosecutions under the 1985 act. Rendell is also pressing for resources to be put into education and awareness campaigns for girls and women to have an informed choice as to whether to submit to the procedure or not.     

轮状病毒疫苗研究现状

轮状病毒自上世纪70年代初发现至今,仍是婴幼儿病毒性腹泻最主要的病原体。每年约60万婴幼儿因轮状病毒感染导致严重脱水死亡。轮状病毒疫苗从上世纪90年代初开始研制,至今已有三种疫苗用于预防轮状病毒感染。这三种疫苗均为减毒活疫苗:其中包括单一血清型Rotarix、罗特威和重组5价疫苗RotaTeq。它们已在全球多国使用,有些国家已将其纳入免疫规划。疫苗的使用使人群轮状病毒感染下降,特别是死亡率明显减少。但也出现了一些问题,因此除了减毒活疫苗,也有一些实验室研究其他形式的疫苗,例如重组疫苗、灭活疫苗等。本文主要介绍轮状病毒疫苗的研究现状,为我国轮状病毒疫苗的研究、使用和推广提供一定理论依据。