Strategies for safe injections.

In 1998, faced with growing international concern, WHO set out an approach for achieving injection safety that encompassed all elements from patients' expectations and doctors' prescribing habits to waste disposal. This article follows that lead and describes the implications of the approach for two injection technologies: sterilizable and disposable. It argues that focusing on any single technology diverts attention from the more fundamental need for health services to develop their own comprehensive strategies for safe injections. National health authorities will only be able to ensure that injections are administered safely if they take an approach that encompasses the whole system, and choose injection technologies that fit their circumstances.

PIP: This article reviews a WHO approach aimed to achieve injection safety that encompasses all elements from patients' expectations and doctors' prescribing habits to waste disposal. Additionally, the paper describes its implications for two injection technologies: sterilizable and disposable. It argues that focusing on any single technology diverts attention from the more fundamental need for health services to develop their own comprehensive strategies for safe injections. National health authorities will only be able to ensure that injections are administered safely if they take an approach that encompasses the whole system and choose injection that fit their circumstances. When national authorities seek to identify the strategy most suited to their needs, they must take account of all three elements: behavior, management, and finance.

Immune response to an intercalated enhanced inactivated polio vaccine/oral polio vaccine programme in Israel: impact on the control of poliomyelitis.

A combined enhanced inactivated polio vaccine (EIPV) and oral polio vaccine (OPV) programme was introduced in Israel in 1990, with the purpose of providing a solution to the persistent polio morbidity in spite of a 30 year long OPV programme. The schedule comprised two doses of EIPV administered at the age of 2 and 4 months, intercalated with two doses of OPV at 4 and 6 months, followed by a reinforcing dose with the two vaccines simultaneously administered at 12 months. The 5-year evaluation of the programme included: the assessment of clinical suspicions of polio, early immune response in successive cohorts administered the new schedule, dynamics of the immune profile in a cohort followed up to the age of 5, and monitoring of wild poliovirus excretion in sewage specimens collected in 25 permanent sites throughout Israel as well as from the Palestinian Authority. No paralytic polio cases associated with a wild or vaccinal poliovirus strain were detected since the introduction of the programme. At the age of 4 months, one week after administration of the second EIPV and first OPV dose, 100% seropositivity and high geometric mean titres (GMTs) of neutralizing antibody (NA) to the three vaccinal and to the wild poliovirus type 1, responsible for the 1988 polio outbreak, were observed. No change in percent of seropositivity occurred between the age of 6 and 12 months. Thirty days after the IPV and OPV reinforcing doses, GMTs to each of the four poliovirus strains were > or = 3037. Up to the age of 5, the seropositivity was unchanged. After a 2.5-10-fold decline in the first year following the completion of the programme, GMTs to the three vaccinal and the wild poliovirus strain levelled off at rather high values, considered protective. Between 1990 and 1995, 16 wild poliovirus type 1 strains were isolated in three separate episodes in Gaza Strip sewage and once only in one Israeli site very close to Gaza City. The rapidly established, high and persistent NA titre to the vaccinal and wild poliovirus strains and the presence of immunological memory are indicative of high individual protection throughout the first 5 years of life. The only one-time introduction, without circulation, of a wild poliovirus strain in a single Israeli settlement suggests community protection. The intercalated programme offers a contribution to polio eradication by providing a solution to the primary and secondary failure associated with OPV, as well as to the control of vaccine-associated paralytic poliomyelitis.

Induction of humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection?

In an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (SIV) infection, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 micrograms of an inactivated preparation of SIV/Delta B670 in either an oil-in-water emulsion with Ribi Detox, containing mycobacterial cell wall skeleton and monophosphoryl lipid A (CWS/MPL) (group A) or a water-in-oil emulsion with incomplete Freund's adjuvant, containing CWS/MPL for the first two injections (group B). Animals were challenged with 10-100 monkey ID50 of monkey-cell-grown SIVmac251 3 months after the last injection, along with a group of four unvaccinated controls. Group B animals demonstrated the strongest immune responses following immunization, including neutralizing antibody titres against the challenge virus ranging from 160 to 320 and SIV-specific ELISA titres ranging from 10(5)-10(6) on the day of challenge, as well as strong in vitro lymphoproliferative and interleukin-2 (IL-2) production responses to the immunogen. Neutralizing antibody was not detectable in group A animals, ELISA titres were lower (10(2)-10(4)), no in vitro lymphoproliferative responses were observed, and in vitro IL-2 production was less pronounced. No protection against challenge was observed in either group. Moreover, group B animals exhibited a more pronounced clinical response following challenge than either group A animals or controls, consisting of hyperthermia and a greater degree of lymphadenopathy on day 7, followed by hypothermia and generally higher levels of serum viraemia on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Can we agree on a prescription? A view from the perspective of the developing countries.

There are serious obstacles, particularly on the African Continent, to the application of the official strategy for eradication of poliomyelitis. Outbreaks in countries where a potent OPV was used keep raising the question of its efficacy in routine programs. Based on the South American strategy, 200 million doses of OPV are needed for the 11 million children born each year. Such quantities of vaccine can hardly be procured for the rest of the world. Organization of vaccination campaigns will be competing with other public health programs. Studies in Africa and in the Middle East have shown the good performance of one or two doses of eIPV combined with DTP. At the current price of the quadruple vaccine DTP-eIPV, its cost effectiveness not only in money, but in practical terms, especially for the inventory, the cold chain, and the delivery, would be extremely attractive.

Immunologic memory induced at birth by immunization with inactivated polio vaccine in a reduced schedule.

One hundred forty-one healthy newborns were immunized 24 hours after birth with one dose of inactivated polio vaccine (IPV) of enhanced potency. Following the administration of a second vaccine dose six months later, a considerable proportion of babies responded with neutralizing antibody (NA) to the three poliovirus types. The very rapid occurrence and high antibody titer were indicative of an anamnestic response. Twenty-one infants who still had NA less than 1:4 to one-more poliovirus types after the second vaccine dose responded with very high NA values 7-10 days after a supplementary dose of IPV. It appears that IPV of enhanced potency administered at birth is apt to induce immunologic memory, which should provide the basis for protection against paralytic poliomyelitis in case of exposure to wild poliovirus later in life.

Use of killed poliovirus vaccine in a routine immunization program in West Africa.

Combined diphtheria-tetanus-pertussis (DTP)-killed poliovirus vaccine was used (along with bacille Calmette-Guérin, measles, yellow fever, and smallpox vaccines) in a routine immunization program in a rural area of Senegal. A control group in a neighboring region received DTP vaccine without poliovirus vaccine. All immunizations were given at two sessions six months apart by a small mobile health team led by a nurse. Six months after the second dose of DTP-polio vaccine, 97.4%, 97.7%, and 90% of subjects two to eight months old at the start had detectable antibody to poliovirus types 1, 2, and 3, respectively. In the control group, 50%, 38%, and 80% of such subjects had antibody to poliovirus types 1, 2, and 3, respectively, acquired by natural infection during the study year. An average of 3.9 cases of paralytic poliomyelitis (range, one to 13) were observed annually at one dispensary in the test region from 1966 through 1979. From 1980 through 1982, since the immunization program has been in effect, only one case has been observed (in a nonimmunized child).

Antigen content of inactivated poliovirus vaccine for use in a one- or two-dose regimen.

The immunologic response to inactivated poliovirus vaccine following one and two doses has been studied in infants in developing and developed countries using vaccine prepared at the Rijks Instituut voor de Volksgezondheit, The Netherlands. Virus was grown in microcarrier cultures of monkey kidney cells, purified, concentrated, and inactivated with formalin. The vaccines used contained different quantities of D-antigen units for each of the three types. The data reveal that both antibody and immunologic memory (booster-type responsiveness) were induced in virtually all individuals following a single dose of a sufficient quantity of antigen. Immunologic memory was readily revealed by the booster-type response following a second dose given six months after the first. The degree of booster-type response to a second dose is linked primarily to the quantity of antigen used for primary immunization, and secondarily to the quantity of antigen used for the booster dose. The data base is presented for formulating the antigen content of an inactivated poliovirus vaccine that can be relied upon to be protective after the first dose when given alone or when incorporated with combinations of other antigens (diphtheria-per tussis-tetanus) that may require two or more doses.

Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis.

This paper contains a summary of the principles upon which the preparation and use of killed poliovirus vaccine (KPV) are based, as well as a summary of earlier and more recent work suggesting the feasibility of formulating a KPV preparation that would be fully and durably effective in a one- or two-dose regimen. The essential factor in the preparation of such a vaccine is the inclusion of a sufficient mass of the immunizing antigen, for each of the three antigenic types of poliovirus, to induce the formation of humoral antibody and/or immunologic memory after the first dose. The results of a series of studies carried out in West African and Scandinavian countries are summarized, which suggest that such a vaccine should contain 40, 8, and 32 D-antigen units for types I, II and III, respectively. If the D-antigen unit measurement is to be used as a guide to KPV standardization, the details of the method of manufacture are important; in this regard, the method of vaccine preparation used at the Rijks Instituut voor de Volksgezondheid should serve as a reference standard for the preparation of vaccines expected to produce the effects described.

Killed poliovirus antigen titration in humans.

To establish the antigen content of a killed poliovirus vaccine sufficiently potent to induce immunity with one or two doses and to establish a reference standard vaccine which has been tested under field conditions, a titration was carried out in infants to determine the amount of each of the three antigenic types of poliovirus vaccine required to induce seroconversion with a single dose. It has been observed that over a critical range of antigen concentration there is an essentially linear relationship between antibody response and quantity of antigen administered. More than 90 percent of the groups studied had detectable antibody after receiving single injections of 80, 8 and 64 D-antigen units of Types I, II and III, respectively. Four-fold less antigen for each of the three types was less effective. The implications of these findings for an efficient immunization procedure are discussed.

[A new strategy of fight against meningococcal meningitis epidemics in Sahelian Africa]. / Une nouvelle stratégie de lutte contre les épidémies de méningites a méningocoques en Afrique Sahélienne.

An acquired sulfamido-resistance to menigococcus having appeared, the authors propose a single injection of a cheap and efficient antibiotic, chloram-phenicol, suspended in oil for cerebrospinal meningitis treatment. This treatment has been successfully applied at the Bobo-Dioulasso hospital (recovery in 82.5% of the cases). Two controlled experiments on the field of the group A polysaccharidic antimeningococcic vaccine in the Koudougou (Haute-Volta) and Koutiala (Mali) areas confirmed its efficiency and innocuity, the conferred immunity persisting two years at least. The appearance of serogroup C meningococcus at the origin of the epidemic attacks in Nigeria 1975 has been confirmed at Niamey (Niger). In consequence of this new experience of the logistic and economic conditions in the countries of the "meningitic belt" the following strategy for meningococcus epidemic control may be proposed:--a strict epidemiologic supervision by nurses in rural dispensaries;--as soon as a few cases are reported in a medical sector, application of the "minute treatment" with chloramphenicol to all meningitic patients, which permits the "lethality prophylaxis"; the national authorities shall be then warned; they will make the diagnostic of the causal serogroup (A or C) thanks to the electroimmunodiffusion technique;--as soon as the serogroup is demonstrated, a specific "circonstance vaccination" campaign for the whole population of the sector shall be carried out, in order to stop the development of the disease.

[Controlled tests of anti-meningococcal polysaccharide A vaccine in the African Sahel area (Upper Volta and Mali) ]. / Essais controles du vaccin anti-meningococcique polysaccharidique a en Afrique de l'ouest Sahelienne (Haute Volta et Mali).

After the first tests of this vaccine in Egypt (1972) and in the Sudan (1973), two controlled tests in the field were performed in two high-risk areas for meningitis: --firstly, in the region of Koudougou (Upper-Volta), in November-December 1973 (17,300 vaccines). Its major aim was to solve operational and logistical problems; --secondly, in the Koutiala (Mali) area, according to a very strict schedule, in November-December 1975 and December 1975 (37,979 vaccines). The complete innocuousness of the vaccine was proven and excellent seroconversion was observed after its administration. On the individual level, it was confirmed that the vaccine ensures excellent protection for a period of at least three years. This new prophylactic weapon inspires the authors to suggest a new strategy in the fight against meningitis epidemics caused by meningococcus in the African Sahel area, taking into account the current increase there in serogroup C, against which there is also a vaccine whose efficacy has already been demonstrated.