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Lancet. 2016 Mar 19; 387:1147.WHO convened a multidisciplinary consultation last week to identify the tools and interventions needed to outsmart the Zika epidemic. Towards the end of the meeting, delegates representing the major regulatory agencies in the USA, Europe, and Brazil, committed to putting Zika-related products on a regulatory fast-track. They also agreed that instead of waiting, as they usually do, for manufacturers to approach them, they would take the initiative and approach companies working on promising products. Their gesture, in a sense, encapsulates the success of the meeting in bringing together so many minds from so many disciplines to focus, for 3 intensive days, on a single issue of vital importance. (Excerpts)
The challenge of Trypanosoma brucei gambiense sleeping sickness diagnosis outside Africa. [Le défi que pose le diagnostic de la maladie du sommeil à Trypanosoma brucei gambiense en dehors de l'Afrique]
Lancet Infectious Diseases. 2003 Dec 1; 3(12):804-808.Sleeping sickness is a lethal African disease caused by parasites of the Trypanosoma brucei subspecies, which is transmitted by tsetse flies. Occasionally, patients are reported outside Africa. Diagnosis of such imported cases can be problematic when the infection is due to Trypanosoma brucei gambiense, the chronic form of sleeping sickness found in west and central Africa. The low number of trypanosomes in the blood and the non-specific, variable symptoms make the diagnosis difficult, particularly when the index of suspicion is low. When the trypanosomes have penetrated into the central nervous system, neuropathological signs become apparent but even at this stage, misdiagnosis is frequent. Rapid and correct diagnosis of sleeping sickness can avoid inappropriate or delayed treatment and even death of the patient. In this article, an overview on diagnosis of imported cases of T b gambiense sleeping sickness is given, and possible pitfalls in the diagnostic process are highlighted. Bioclinical parameters that should raise the suspicion of sleeping sickness in a patient who has been in west or central Africa are discussed. Techniques for diagnosis are reviewed. A clinician suspecting sleeping sickness should contact a national reference centre for tropical medicine in his or her country, or the WHO, Geneva, Switzerland, or the Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA, for clinical consultation and provision of specific diagnostic tests. Appropriate drugs for sleeping sickness treatment are also provided by WHO and the CDC. (excerpt)
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1991; 69(3):277-83.The frequent reactivation of disease in immunosuppressed patients represents a serious health complication for acquired immunodeficiency syndrome (AIDS) patients with herpesviruses. Since the herpesviruses are often associated with the development of complication such as pneumonia and lymphoma, an emphasis is being placed on the rapid laboratory diagnosis of herpes simplex viruses 1 and 2, varicella- zoster, Epstein-Barr virus, and cytomegalovirus. Diagnostic methods that utilize monoclonal antibodies to detect viral antigens in clinical specimens are now within the scope of general laboratories and detection methods for viral DNA in clinical specimens are being advanced. Each of the viruses requires its own diagnostic procedures, however, and consideration should be given to practical and economic issues. The World Health Organization (WHO) has recommended that developing countries use rapid diagnostic techniques that do not require expensive, labor-intensive virus replication. Serological diagnosis can facilitate disease surveillance of the herpesviruses in different population groups in countries with little information on this infection's epidemiology. Who is recommending that regional or national reference laboratories establish confirmatory testing facilities to support the routing virological or microbiological services offered by local laboratories. Other WHO recommendations include the development of international standard preparations and reference reagents, compilation of a list of monoclonal antibodies available for collaborative diagnostic studies, and promotion of studies on the rapid diagnosis of herpesvirus-promoted encephalitides.
In: International Conference on the Implications of AIDS for Mothers and Children: technical statements and selected presentations jointly organized by the Government of France and the World Health Organization, Paris, 27-30 November 1989. Geneva, Switzerland, WHO, Global Programme on AIDS, 1989. 23-4. (WHO/GPA/DIR/89.12)Large gaps exist in knowledge of the clinical, immunologic, and virologic correlates of human immunodeficiency virus (HIV) transmission from infected mothers to their infants. Physiological changes in the immune system of pregnant women as well as maternal antibodies to certain virus-encoded proteins may affect the natural history of HIV infection. Also relevant may be the stage of the mother's infection and the time of HIV transmission to the fetus. There is some evidence that maternal antibodies to the immunodominant hypervariable loop in gag protein 120 may reduce the risk of transmission to the fetus. More basic research in virology and immunology is needed for the development of prophylactic and therapeutic approaches to maternal-infant HIV infection. Research priorities include the following: the impact of pregnancy on clinical outcome and virological and immunologic markers in HIV-infected women; correlates of perinatal transmission such as virus characteristics and load, neutralizing antibodies, and cell-mediated immunity; possible immunologic or chemotherapeutic interventions to decrease perinatal transmission; and the standardization of virologic and immunologic markers for pediatric HIV infection.
Clinical and Experimental Immunology. 1978 Aug; 33(2):360-375.Since guidelines for safety evaluation of antifertility vaccines do not exist, this WHO report attempts to define the parameters to be examined and the methodology which might be used for such a safety assessment. In principle, antifertility vaccines may: 1) prevent sperm transport and/or fertilization; 2) prevent or disrupt implantation; and 3) prevent blastocyst development. Potential advantages of this immunological approach to fertility regulation include: 1) possibility of infrequent administration, possibly by paramedicals; 2) use of antigens or antigen frangments that are not pharmacologically active; and 3) the possibility of large-scale synthesis and manufacture of vaccine at relatively low cost in the case of antigens of known chemical structure. To evaluate the efficacy and safety of placental antigen vaccines, placental antigens used should not possess significant immunological similarity with tissue other than placenta. Carriers or haptens may require structural remodifications of placental molecules to overcome natural immunological tolerance. Adjuvants may be needed to enhance the immune response required. Quality-control procedures for vaccine component production include tests for: 1) purity; 2) toxicity; 3) sterility; and 4) shelf-life. Acute, subacute, and chronic toxicity testing in animals is described for it must be performed separately for the haptenated antigen or conjugate and adjuvant. Such tests would include hematological parameters, blood chemistry, urinanaylsis, gross pathological and organ weight analysis, and ophthalmological tests. Animal models are suggested. Means of monitoring the immune reponse and potential hazards of immunization (e.g., allergy or autoimmune disease) are discussed. The rationale and protocol for safety and efficacy studies of human chorionic gonadotropin-peptide vaccine receive similar attention, with emphasis on tests to be performed before human clinical trials can start.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1993; 71(5):641.Oral fluids are a mixture of saliva and oral mucosal transudates (OMT). Saliva is a product of the salivary glands and contains mostly IgA, while OMT is mostly fluid in the subgingival space derived from the passive transport of plasma and contains mostly IgG. The IgG concentration, however, is much lower than that in serum. Testing for antibodies to HIV in oral fluids has been proposed as an alternative to antibody testing in blood. The fluids may be collected directly by dribbling into a receptacle and via absorption onto pads using specially designed collection devices. Only one commercially available HIV antibody test is, however, specifically designed for use with oral fluid samples. Some existing commercial tests designed to detect antibody to HIV in blood samples have been modified for use with oral fluids, but only limited information is available on their performance. Several studies suggest that using tests to detect HIV antibodies in oral fluids may be adequate for some situations, but a number of issues remain to be addressed. WHO therefore recommends that a full evaluation of the detection of HIV antibody in oral fluids be undertaken to address the issues before recommendations on HIV antibody testing using oral fluids are made. Such evaluation would gather information on the accuracy and cost-effectiveness of testing oral fluids. Ethical considerations when performing HIV testing using oral fluids would be the same as those for blood: non-coercion, informed consent, counseling, and confidentiality.
WHO international quality assessment scheme for HIV antibody testing: results from the second distribution of sera.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1992; 70(5):605-13.The WHO international quality assessment scheme for human immunodeficiency virus (HIV) antibody testing has been established to monitor the quality of laboratory performance in testing for antibodies to HIV. Following a small trial distribution of specimens early in 1989, the second distribution was made in February 1990. A total of 20 specimens of sera, 10 of which contained antibodies to HIV-1, were sent to 103 laboratories located in the 6 WHO Regions. Participants were asked to report to WHO their findings on each specimen for each diagnostic assay used and their interpretation of the HIV antibody status of each specimen. For the antibody-positive specimens; 98.2% of the results were interpreted as positive and 1.8% as indeterminate; no false-negative interpretations were reported. For their antibody-negative specimens, 90.3% of the results were interpreted as negative, 1.3% as positive, and 8.4% as indeterminate. Most of the indeterminate reports were associated with one particular specimen. A wide variety of diagnostic assays and combinations of assays were used. In terms of the technical results obtained rather than their interpretation, the assays appeared extremely reliable for the positive specimens, with 99.5% of assay results being recorded as positive, 0.17% as negative, and 0/34% as indeterminate. There were more errors associated with the negative specimens: 93.5% of assay results were recorded as negative, 3.5% as positive, and 3% as indeterminate. However, ;61% of the false-positive and indeterminate assay results obtained with the negative specimens were associated with only 2 specimens. There were considerable variations in the Western blot patterns reported and a variety of different interpretative criteria were applied to them. (author's)
PROGRESS IN HUMAN REPRODUCTION RESEARCH. 1992; (22):4-5.During 1986-1988, the WHO Special Programme of Research, Development and Research Training in Human Reproduction used the diphtheria toxoid as a carrier for a fragment of the human chorionic gonadotropin (hCG) molecule (a conjugate immunogen) and an immunostimulant in a phase I clinical trial of this prototype antifertility vaccine in sterilized women. Between 1990 and 1991, it conducted teratology studies in rats and rabbits to determine whether the vaccine causes fetal abnormalities. The vaccine did not adversely affect either the animals or their fetuses. Clinical trials of the vaccine's effectiveness (phase II trials) are scheduled for 1992. At least 2 injections several weeks apart, are needed to produce an anti-hCG immune response which is only effective for 3-6 months, however. So the same components of the original vaccine were placed in a polymer to deliver the vaccine slowly over a prolonged and predetermined time frame. WHO hoped that this advanced vaccine would raise effective immunity levels long enough to last for at least 1 year after 1 injection. WHO is conducting dose-response and toxicity studies of this prototype vaccine in rabbits and baboons to identify the optimal dose which would elicit an effective immunity level over a desired period of time and would be safe for testing in humans. WHO hopes to begin a phase I clinical trial with this advanced anti-hCG vaccine in late 1992. WHO anticipates that the preclinical and clinical trials will reveal a need for further modifications and improvements. WHO is supported multicenter research on antitrophoblast vaccines which target membrane cells of the preimplantation embryo since 1985. It uses monoclonal antibodies (MABs) and recombinant DNA technology to identify and isolate surface molecules. So far this research has tested 15,000 MABs but is centering on 9 MAbs. A study in baboons showed that 1 MAB reduced fertility, even though researchers could only use minute amounts of the protein in the injection.
Lancet. 1992 May 30; 339(8805):1355-6.Researchers compared the immune responses of infants vaccinated at 2, 3, and 4 months of age with the diphtheria-pertussis-tetanus (DPT) conjugate vaccine with those of infants vaccinated at 3, 5, and 9 month intervals. The antibody titer for pertussis was the same for both the old and new schedules. Further, no reliable immunological correlates of protection existed for pertussis. Different batches of DPT vaccine and maternal antibodies may have accounted for the variation in immune responses. No one measured maternal antibodies in the infants in the 3, 5, and 9 month group, though. The protective level of antitoxin for tetanus and diphtheria (0.01 neutralizing units/ml) cannot be applied to ELISA assays, since the relationship between the 2 assays is inadequate at levels less than 0.1 IU/ml. 1964 research of 9 injection schedules showed that when infants received the first dose at 3 months rather than later, or when the intervals were 1 month long instead of 2 months, diphtheria and tetanus antitoxin titers were lower 2 weeks after series completion. Therefore, clinical researchers should do lengthy longitudinal studies of infants vaccinated at 2, 3, and 4 months before the clinicians can actually determine the persistence of immunity to school entry. The UK Public Health Laboratory Service is doing a longitudinal study of early and long term antibody responses to the new schedules. In fact, the accelerated vaccination schedule has improved coverage during the first year of life. 20-30% of pertussis cases are less than 6 months old in developing countries. WHO's Expanded Programme on Immunization encourages health workers to begin vaccine series as early in life as possible and to keep the intervals as short as possible. Even though no primary series of 3 doses of DPT protects an infant for a lifetime, health workers should achieve high coverage with early doses and shorter intervals. WHO already advocates giving women of reproductive age in developing countries 5 doses of tetanus toxoid to reduce neonatal deaths.
WHO laboratory manual for the examination of human semen and semen-cervical mucus interaction. 2nd ed.
Cambridge, England, Cambridge University Press, 1987. , 67 p.The WHO Special Programme of Research, Development and Research Training in Human Reproduction has revised its manual designed to standardize procedures for the examination of human semen. This revised manual, for instance, describes a simplified method for screening the morphology of cellular elements other than spermatozoa; the previous method now appears in the section on optional procedures. WHO has also included methods to determine the presence of spermatozoa antibodies. The manual has guidelines on measurement of biochemical components of seminal plasma to evaluate the secretory function of accessory glands (e.g., fructose indicates secretory function of the seminal vesicles). Even though these biochemical tests may not mark a man's fertility, they demonstrate the functional state of these glands. Besides, someday they may even help assess the possible effects of xenobiotic factors and of disease. Some researchers believe adenosine triphosphate levels are linked to spermatozoal function and that the zona free hamster oocyte test can determine the ability of human spermatozoa to join with the oocyte; so WHO has listed protocols for these 2 tests. The manual also has protocols to assess the ability of spermatozoa to penetrate cervical mucus in vitro: the microscopic method and the capillary tube test. WHO believes that determining this ability is important when evaluating the fertility of a couple. The Standard Procedures section on collection and examination of human semen considers appearance, volume, consistency, pH, motility, preparation and grading, agglutination, sperm viability, sperm count, and testing for antibody-coating of spermatozoa. The section on sperm cervical mucus interaction examines volume, consistency, ferning, spinnbarkeit, cellularity, pH, and in vivo and in vitro tests. It hopes that researchers will adapt the standard procedures presented in this manual to improve quality control between laboratories and allow aggregation of data from several sources for analysis.
NETWORK. 1992 Aug; 13(1):20-3.Researchers are pursuing 2 approaches to developing a male contraceptive drug. 1 approach centers around suppression of sperm production the other around blocking conception. Researchers are looking at introducing hormonal contraceptives into men's bodies via injections or implants to stop sperm production. Both forms of these possible male contraceptives will not be available for many years, however. A WHO study on testosterone enanthate of men in 7 countries reveals total suppression of sperm production occurred in almost all the Asian men, but only about 60% suppression occurred in other ethnic groups. A current WHO study is examining whether a hormonal contraceptive which is not 100% effective can be useful if it would be more effective than barrier methods. The Population Council is conducting research on 2 capsule implants with 1 capsule releasing luteinizing hormone releasing hormone 13 to halt sperm production while the other releases an androgen to maintain sex drive. Animal tests indicate complete contraception with no side effects. The other possible means of suppressing sperm production is administration of a cottonseed oil extract called gossypol which appears to stop sperm production thereby eliminating the need for concurrent androgen administration. Yet it does cause potassium depletion in some men which can result in arrhythmias. An antifertility vaccine comprises the 2nd approach. Several US researchers are exploring an antifertility vaccine to produce antibodies only to the specialized sperm surface needed to attach to the egg. The 1st antifertility vaccine would probably be in pill form and a woman's contraceptive since it is earlier to target the smaller number of sperm in the oviduct than in the testes.
In: Vaccines for fertility regulation: the assessment of their safety and efficacy. Proceedings of a Symposium on Assessing the Safety and Efficacy of Vaccines to Regulate Fertility, convened by the WHO Special Programme of Research, Development and Research Training in Human Reproduction, Geneva, June 1989, edited by G.L. Ada, P.D. Griffin. Cambridge, England, Cambridge University Press, 1991. 5-11. (Scientific Basis of Fertility Regulation)The predecessor of the WHO Task Force on Vaccines for Fertility Regulation chose to commit most of its resources to research and development of a vaccine directed against human chorionic gonadotropin (hCG). Task force members made this choice in 1978 because scientists tended to already know the amino acid sequence and general structure of hCG and a vaccine against hCG would prevent implantation of the fertilized ovum. Specifically they focused on the unique sequence of C-terminal 37 amino acid peptide of the beta chain of hCG because this method would not allow production of antibodies cross reacting with human luteinizing hormone and would reduce the risk of autoimmune pathology and other effects of cross reactivity of antibodies. They also defined the various parameters and the methodology to assess the safety of the approach which still is a useful guide to development of hCG and other antifertility vaccines. The Task Force strongly recommended that target antigens should be temporary and in relatively low amounts and limited to gametes and/or early products of fertilization. A Phase I clinical trial in sterilized women has already been conducted and a limited efficacy trial in fertile women is planned. In June 1989, WHO hosted a symposium in Geneva, Switzerland to review the safety and efficacy of antifertility vaccines based on past and current research and development. This symposium focused much attention on immunological and endocrine considerations. WHO forecasted that recommendations coming from the symposium would not only guide future research on vaccines against self-antigens but maybe even antitumor vaccines.
WORLD HEALTH. 1991 Sep-Oct; 12.A researcher with WHO's Tropical Disease Research Programme reviews techniques used to diagnose malaria. Present techniques have not improved much since a French physician 1st used a microscope in 1880 to examine blood from a sick soldier and then noticed the parasites of Plasmodium falciparum. Yet optical quality has improved and special stains can now be used to color the parasites making them more recognizable. In fact, at a magnification of 600-700 times, a scientist can identify all 4 plasmodia, the blood forms of the plasmodia, and count the plasmodia. Blood samples and a microscope allow physicians to monitor the ill person's progress after they began treatment. Yet a microscope and the needed laboratory skills and other resources are not always present in health center in a village in countries where malaria is endemic. It is here where simple and effective techniques are needed the most. 1 approach is to detect antibodies to the plasmodia, but this takes much time. In addition, antibodies are only present after an individual has been infected for a relatively long time. Thus this technique cannot detect malaria early enough to provide proper treatment. Another approach readily identifies antigens. Yet the techniques required are complicated and require a lot of time. Besides antigen techniques are not as reliable as microscopic diagnosis. Researchers are presently experimenting on simple visual methods which are quick, inexpensive, and reliable. Molecules in the plasmodia which are in a small amount of blood will either react or not react with reagents incorporated on a dipstick or card. Thus physicians can detect what plasmodia are present and estimate parasite load. Another test can inform the physicians what antimalarial to prescribe and how much and resistance of the plasmodia to the antimalarial.
ANNALS OF TROPICAL PAEDIATRICS. 1989 Mar; 9(1):1-5.A total of 177 children seen at 2 hospitals in Kampala are described who were strongly suspected of having acquired immunodeficiency syndrome (AIDS), either on clinical grounds or because they fulfilled WHO case- definition criteria for diagnosis of pediatric AIDS. Blood was taken from the 177 children and 154 of their mothers and tested for antibody to human immunodeficiency virus (HIV) by an enzyme-linked immunoassay (ELISA). Altogether, 119 (67%) children were seropositive, but only 85 (71%) fulfilled the WHO case-definition criteria, and they were significantly older than the 34 who did not fulfill the criteria. A further 58 children were seronegative but fulfilled the WHO criteria. Of the 119 seropositive children, only 3 had a history of previous blood transfusion, but 103 (98%) of 105 mothers were HIV seropositive: consequently, their children were considered to have been infected in utero or perinatally. 13 (26%) of 49 mothers of seronegative children were seropositive. 80% of HIV-infected children were under 2 years of age at diagnosis and 23% died within 3 months of diagnosis. None of the parents was known to be an intravenous drug user, a prostitute, or bisexual. The difficulty of accurate diagnosis of AIDS presents a major problem in Africa, as the WHO clinical case-definition criteria alone are clearly not adequate. (author's)
JAMA. 1988 Dec 9; 260(22):3286-9.In Africa, as in many developing countries where AIDS has been documented, the specific serologic test for antibody to the human immunodeficiency virus is not feasible, and the case definition of the Centers for Disease Control is impracticable because facilities for diagnosing the opportunistic infections are inadequate and the clinical spectrum of AIDS is different in tropical countries. The World Health Organization developed a clinical case definition at a 1985 AIDS workshop in the Central African Republic. It was tested to determine its generalizability in Zaire, and the present paper is a report on experience using the definition to identify AIDS in Uganda. A clinical case of AIDS is defined by the presence of at least 2 major signs and 1 minor sign. The major signs are fever for more than 1 month, weight loss greater than 10%, and chronic diarrhea for more than 1 month. The minor signs are persistent cough for more than 1 month, pruritic dermatitis, herpes zoster, oropharyngeal candidiasis, ulcerated herpes simplex, and general lymphadenopathy. The presence of disseminated Kaposi's sarcoma or disseminated cryptococcosis is sufficient by itself to diagnose AIDS. The Uganda study included 1328 patients at 15 hospitals. 562 patients (42%) tested positive by enzyme-linked immunosorbent assay, and 776 (58%) tested negative. 424 patients (32%) met the world Health Organization clinical case definition for AIDS. The World Health Organization definition had a sensitivity of 55%, a specificity of 85%, and a positive predictive value of 73%. However, so many of the patients in this sample had active tuberculosis that it was decided to substitute "persistent cough for more than 1 month without concurrent tuberculosis" as a minor sign in place of "cough for longer than 1 month." With this modification 350 patients met the clinical case definition for AIDS. Sensitivity dropped to 52%, but specificity rose to 92%, and positive predictive value rose to 83%. Moreover, 26% of the seropositive females indicated amenorrhea as a symptom. Addition of amenorrhea to the modified case definition gave it a sensitivity of 56%, a specificity of 93%, and a positive predictive value of 86%. However, this is the 1st report of amenorrhea as a symptom of AIDS, and it may only be a symptom of severe weight loss in women of childbearing age. The findings in the Ugandan experience support the generalizability of the modified World Health Organization clinical case definition of AIDS and its use for surveillance purposes in Africa.
[Unpublished] 1987 Apr 30. , 53 p.Neonatal tetanus, caused by the toxin of Clostridium tetani, is transmitted via unclean instruments used to cut the umbilical cord or contaminated dressings applied to the stump. The symptoms are inability to suck, trismus, convulsions, and (in 80-90% of cases) death on the 7th or 8th day. In the US between 1982 and 1984 only 2 cases of neonatal tetanus were reported; in the developing world an estimated 800,000 infants die of neonatal tetanus every year. The survey methodology used to determine the neonatal tetanus death rate was a 2-stage sampling method, known as the Expanded Program on Immunization 30 cluster sampling method, followed by questionnaires. Such surveys contain a certain amount of built-in bias due both to fact that the final selection of households is never completely random and that retrospectively gathered information is subject to recall bias. The surveys indicated that neonatal tetanus incidence was highest in rural areas, especially where animals were present; in the slums of cities; among families with many children; where mothers received no prenatal care; and where birth attendants were untrained. The best preventive strategy against neonatal tetanus is provided through immunization of the mother with tetanus toxoid, since the antibodies cross the placenta and protect the infant through the neonatal period. Unfortunately, the tetanus vaccination program lags at least 30% behind other World Health Organization Expanded Program on Immunization coverage. The World Health Organization recommends an initial immunization with .01 antitoxin International Units per milliliter of serum, a 2nd dose 4 weeks later (at least 2 weeks before delivery) and booster doses on each successive pregnancy up to 5; the 5th booster provides lifetime protection. Immunization should also be carried out among nonpregnant women of childbearing age and children. The World Health Organization has proposed that neonatal tetanus be made a reportable disease, which should be combatted by prenatal immunization of mothers and training of traditional birth attendants. Between 60% and 80% of all births in developing countries are attended by traditional birth attendants, but, except in China, the training of traditional birth attendants has not contributed as much to reduction of neonatal tetanus as has immunization. Alternative strategies for carrying out tetanus immunization programs include integrating them into prenatal clinics, schools, family planning programs, maternal food distribution programs, well-baby care centers, mass campaigns (especially in urban areas), and mobile team outreach strategies in rural areas. Tetanus immunization could also be linked to other Expanded Program on Immunization programs even though these are mainly targeted at children rather than mothers and other women of childbearing age. Indonesia initiated a tetanus immunization program in 1977 and a traditional birth attendant training program with assistance from the UN Childrens Fund in 1978. However, 3 neonatal tetanus surveys, conducted in 19 provinces, the city of Jakarta, and Java, estimated the total number of deaths/year from neonatal tetanus as 71,150--a neonatal tetanus mortality rate of 11/1000. 3 provincial level studies, also using the Expanded Program on Immunization 30 cluster sampling method, in Nusa Tenggara Barat, West Sumatra Province, and Daerah Istemewah Aceh revealed neonatal tetanus mortality rates of 8.3/1000, 18.5/1000, and 8.4/1000 respectively. In the Health portion of Indonesia's 4th 5-year plan (Pelita IV), the 1st priority is given to reducing the neonatal death rate of 93/1000 live births; the 7th priority is reduction of mortality due to neonatal tetanus by ensuring adequate immunization as part of routine health services and by requiring 2 tetanus immunizations of all women applying for a marriage certificate.
Washington, D.C., National Academy Press, 1988. x, 239 p.The Committee for the Oversight of AIDS Activities presents an update to and review of the progress made since the publication 1 1/2 years ago of Confronting Aids. Chapter 1 discusses the special nature of AIDS (Acquired Immunodeficiency Syndrome) as an incurable fatal infection, striking mainly young adults (particularly homosexuals and intravenous drug users), and clustering in geographic areas, e.g., New York and San Francisco. Chapter 2 states conclusively that HIV (Human Immunodeficiency Virus) causes AIDS and that HIV infection leads inevitably to AIDS, that sexual contact and contaminated needles are the main vehicles of transmission, and that the future composition of AIDS patients (62,000 in the US) will be among poor, urban minorities. Chapter 3 discusses the utility of mathematical models in predicting the future course of the epidemic. Chapter 4 discusses the negative impact of discrimination, the importance of education (especially of intravenous drug users), and the need for improved diagnostic tests. It maintains that screening should generally be confidential and voluntary, and mandatory only in the case of blood, tissue, and organ donors. It also suggests that sterile needles be made available to drug addicts. Chapter 5 stresses the special care needs of drug users, children, and the neurologically impaired; discusses the needs and responsibilities of health care providers; and suggests ways of distributing the financial burden of AIDS among private and government facilities. Chapter 6 discusses the nomenclature and reproductive strategy of the virus and the needs for basic research, facilities and funding to develop new drugs and possibly vaccines. Chapter 7 discusses the global nature of the epidemic, the responsibilities of the World Health Organization (WHO) Global Program on AIDS, the need for the US to pay for its share of the WHO program, and the special responsibility that the US should assume in view of its resources in scientific personnel and facilities. Chapter 8 recommends the establishment of a national commission on AIDS with advisory responsibility for all aspects of AIDS. There are 4 appendices: Appendix A summarizes the 1986 publication Confronting Aids; Appendix B reprints the Centers for Disease Control (CDC) classification scheme for HIV infections; Appendix C is a list of the 60 correspondents who prepared papers for the AIDS Activities Oversight Committee; and Appendix D gives biographical sketches of the Committee members.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1985; 63(2):241-8.The WHO memorandum outlines the present situation regarding pertussis vaccines, discusses ways to evaluate candidate vaccines, and identifies future research needs. Most existing whooping cough vaccines are whole-cell vaccines, combined with diphtheria and tetanus toxoid adsorbed on an aluminum or calcium carrier. As whole bacterial cells, they contain a complex array of at least 7 toxins and antigens, and display a narrow margin between potency and toxicity. The Japanese introduced an acellular vaccine, admittedly sometimes less potent, called the Precipitated Purified Pertussis Vaccine, in 1981. This material contains far less bacterial mass, notably less endotoxin, and consequently produces less fever, erythema and induration. WHO has not yet established minimum requirements for standardization; even the mouse potency assay may not be suitable. There are techniques, however, which will measure amounts of component antigens and toxicity. Conflicting results on assays of potency and immunogenicity will have to be resolved. Besides the obvious need for large clinical trials of defined vaccines, a whole range of research needs were suggested, from genetic studies of the organism to specific details of the host response. It is generally agreed that a less reactogenic and more effective pertussis vaccine is needed and feasible.
[Record of the second meeting of the WHO Collaborating Centers on AIDS] Deuxieme reunion des centres collaborateurs de l'OMS pour le SIDA: memorandum d'une reunion de l'OMS.
BULLETIN OF THE WORLD HEALTH ORGANIZATION. 1986; 64(2):221-31.Participants at the 2nd meeting of World Health Organization (WHO) collaborating centers on AIDS (acquired immune deficiency syndrome) held in Geneva in December 1985 reported on progress since the 1st meeting in September 1985 and made a number of recommendations for future action in the areas of information, education, and prevention; reference reactants and tests of anti-HTLV-III antibodies; epidemiologic evaluation; and research on vaccines and antiviral agents. It was recommended that ministries of health, education, and social services provide the public with timely and accurate information on AIDS, that physicians, nurses, and similar personnel inform the ill and the public about AIDS and its prevention, and that school age children and young people be informed about AIDS and how to avoid infection. Systems of registration of AIDS cases should be implemented in order to provide the WHO and member states with data on the international level. Standardization and availability of serologic tests is also required. Instructions for avoiding infection should be provided for health personnel and others caring for AIDS patients, for individuals providing personal services to the public, and to ensure adequate methods of disinfection. Instructions for preventing AIDS should discuss sexual and parenteral transmission as well as perinatal transmission. Specific recommendations for education and family placement for children with AIDS have already been published. Instructions should be provided for prisons and similar estabilshments. Requiring international travellers to provide certificates attesting to their AIDS-free status is not justified as a preventive measure. The significant existing demand for reference reactants including human serums with anit-HTLV-III antibodies and controls is being addressed by several institutes in different countries, but it would be premature to furnish reference reactants other than serums. The WHO collaborating centers should furnish materials for purposes of training in diagnostic techniques. Existing tests for diagnosis and confirmation should be imporved and new tests should be developed, with particular attention to simple methods appropriate for use in developing countries. It will be necessary to establish international biological standards for the HTLV-III virus, but the required specifications are not yet known. Technical cooperation and epidemiological evaluation must be planned separately, based on the different prevalence of infections and technical expertise of different countries. A clinical definition of AIDS is needed for countries lacking resources needed to apply the Centers for Disease Control/WHO definition. Surveillance methods and laboratories can be installed with WHO assistance, to help evaluate the extent of AIDS infection in different countries. Later technical cooperation in the areas of continued surveillance and laboratory capacities will depend on results of the initial evaluation in each country. Research is currently underway in several countries of possible vaccines and drugs. Careful preclinical studies should be done to evaluate the toxicity of an agent before clinical studies are conducted. Convenient animal models should be sought for future research. 3 annexes to this report specify methods of disinfection; general principles of preventing transmission of the AIDS virus through parenteral exposure or following donation of organs, sperm, or other tissue; and a proposed definition of clinical cases of AIDS.
Sequelae of vasectomy. Report of a Meeting on Vasectomy, organized by the Special Programme of Research, Development and Research Training in Human Reproduction held at WHO, Geneva, 3-6 August 1981.
Contraception. 1982 Feb; 25(2):119-23.In response to enquiries received by the World Health Organization (WHO) from several countries, the WHO Special Program of Research, Development and Research Training in Human Reproduction convened a meeting of experts in Geneva during August 1981 to review the available animal, clinical, and epidemiological data on vasectomy, with particular emphasis on clinical implications of longterm sequelae of vasectomy in cardiovascular disease. The occurrence of circulating antibodies to sperm antigens has been demonstrated after vasectomy in all animal species studied thus far by various techniques. Prospective clinical studies of vasectomized and nonvasectomized men have been conducted at 4 centers in the U.S. involving clinical and laboratory evaluation of subjects before surgery and at intervals thereafter. A total of 412 vasectomized men were enrolled in these studies; most were followed for 2, 3, or 4 years. The only significant finding was the development of antibody to sperm antigens. Alexander and Clarkson first reported that vasectomy increases the extent and severity of diet-induced atherosclerosis in cynomolgus monkeys. In a 2nd study, Clarkson and Alexander extended their previous findings to evaluate the effects of vasectomy on naturally occurring atherosclerosis in rhesus monkeys. The mechanism by which vasectomy exacerbates atherosclerosis in monkeys has not been defined. At present epidemiological data which have been published come from observations in the U.S. and United Kingdom and in particular from 2 studies involving 4830 and 1764 vasectomized men studied at about 5-6 years after surgery. No health risks of vasectomy were detected in these early years. Other epidemiological projects are in progress in the U.S. Various options were discussed for further epidemiological studies which might be conducted in developing countries where large numbers of men have been vasectomized. The cohort approach and the case control method, the 2 main study options, are briefly reviewed.
Bulletin of the World Health Organization. 1978; 56(2):179-192.Strong evidence that specific immunogenic components of the reproductive system exist that are not represented in other body systems has led to efforts to develop an acceptable vaccine for fertility regulation. The aim is to create a vaccine administered infrequently by trained technicians outside the clinical environment. For safety and practical reasons, an approach using active immunization with a vaccine is preferred to passive immunization with antibodies. In current research with sperm antigens, a lactate dehydrogenase isoenzyme (LDH-X), an enzyme normally present on the sperm surface, reduced fertility in mice and rabbits. However, significant embryo mortality occurred. Other sperm antigens have been tested and rejected. Most of the research on ovum antigens is directed toward the zona pellucida, and work is in progress to isolate experimental quantities of specific zona pellucida antigens. Antibodies to human zona are reported to react with pig zona and vice versa, providing a model system. Antibodies to whole-placenta homogenates reportedly disrupt pregnancy in several laboratory animal species, and 2 placenta-specific proteins are potential antigens since antibodies to them do not react with any other tissue so far tested. Of 3 protein hormones isolated from placental tissue, 2 are potential antigens. The possible hazards of antifertility vaccines can be divided into 2 categories: problems related to immunization and problems caused by antibodies produced.
Acta Paediatrica Scandinavica. 1978 September; 67(5):553-582.6 research articles plus an introduction constitute this review of present knowledge of lactation and its effects. The superiority of human milk as compared with milk of other origin for feeding newborns, term or preterm, was analyzed in terms of biological development related to digestive, metabolic, and excretory functions during fetal and postnatal life in the 1st article. WHO, concerned with the declining breast feeding rate in developing countries, has organized investigations in 9 different countries of different aspects of breast feeding and breast milk with the aim of formulating programs of intervention. Basic epidemiological data on 24,000 mother/child pairs have just been reported in a preliminary manner, emphasizing socioeconomic differences. The 3rd study investigated the nitrogen and protein components of human milk; the true protein content of human milk is .9% in both well-nourished and malnourished mothers. The next study reviewed lipid and trace element composition of human milk in relation to ethnic variables. Contaminants in human milk are characterized in the next review, with DDT and PCBs the most outstanding. The final article emphasizes new knowledge in human milk immunoglobulin, the most predominant of which is secretory IgA.
In: World Health Organization (WHO). World Health Organization expanded programme of research, development, and research training in human reproduction: fourth annual report. Geneva, Switzerland, WHO, November 1975. 51-5. (HRP/75.3)2 years ago an exploratory program of possible vaccines for birth control was initiated. The approach is totally new and it is impossible to predict the outcome. Research on placental antigens has focused on the beta subunit of human chorionic gonadotropin (HCG), a placental-specific protein called SP1, a placental-specific glycoprotein called PP5, and several protein conjugates and adjuvants which use the beta chain of insulin with carrier proteins to synthesize beta-HCG. Details of this research are given. Considerable data suggest that antibodies to several substances in spermatozoa may immobilize, agglutinate, or destroy their biological activity. Sperm enzyme antigens being investigated include lactic dehydrogenase-X, hyaluronidase, and acrosin. These are given to the female; tests have shown fertility reductions up to 50%. Sperm membrane antigens are difficult to isolate but may be more suitable immunogens since they are membrane bound and would not have the problems of circulating immune complexes or nonspecific tissue cross-reactivity. These include "T" and "S" antigens, sperm immobilizing antigen, and carbohydrate antigens. Various antigen/carrier/adjuvant combinations will also be evaluated. Zona pellucida antigens are another research target, especially zone surface antigens. A workshop was organized to consider the production of local immunity in the female genital tract. Since infertility in humans attributed to immunological factors may hold useful information, a bank of sera from infertile men and women has been established in Arhus, Denmark. A symposium on immunological methods of fertility regulation was held in Bulgaria and the papers published as a monograph.
REVIEWS OF INFECTIOUS DISEASES. 1983 May-Jun; 5(3):452-9.This summary of the worldwide impact of measles discusses epidemiology, reported incidence, clinical severity, community attitudes toward measles, and the impact of immunization programs on measles. Measles, 1 of the most ubiquitous and persistent of human viruses, occurs regularly everywhere in the world except in very remote and isolated areas. Strains of measles virus from different counties are indistinguishable, and serum antibodies from diverse population have identical specificity. Yet, the epidemic pattern, average age at infection, and mortality vary considerably from 1 area to another and provide a contrasting picture between the developing and the developed countries. In the populous areas of the world, measles causes epidemics every 2-5 years, but in the rapidly expanding urban conglomerations in the developing world, the continuous immigration from the rural population provides a constant influx of susceptible individuals and, in turn, a sustained occurrence of measles and unclear epidemic curves. In the economically advanced nations, measles epidemics are closely tied to the school year, building up to a peak in the late spring and ceasing abruptly after the summer recess begins. Maternal antibody usually confers protection against measles to infants during the 1st few months of life. The total number of cases of measles reported to WHO for 1980 is 2.9 million. Considering that in the developing world alone almost 100 million infants are born yearly, that less than 20% of them are immunized against measles, and that various studies indicate that almost all nonimmunized children get measles, less than 3 million cases of measles in 1980 is a gross underestimate. There was adecrease in the global number of reported cases of measles during the 1979-80 period due primarily to the reduction in the number of cases in the African continent and, to a lesser extent, in Europe. It is premature to conclude that such a reported decline is real and that it reflects the beginning of a longterm trend. The contrast between the developed and the developing worlds is most marked in relation to the severity and outcome of measles. Case fatality rates of more than 20% have been reported from West Africa. It has been estimated that 900,000 deaths occur yearly in the developing world because of measles, but data available to WHO indicate that the global case fatality rate in the developing world approaches 2% (in contrast to 2/10,000 cases in the US), and the actal mortality may be greater than 1.5 million deaths per year. The advent of WHO's Expanded Program on Immunization has brought about an awareness of the measles problem. Whenever and wherever measles vaccine has been used effectively on a large scale, a marked reduction in the number of cases has been recorded.