Evaluation of unmodifiable and potentially modifiable factors affecting peripheral intravenous device-related complications in neonates: a retrospective observational study.

OBJECTIVES: Infants in neonatal units benefit from dependable peripheral intravenous access. However, peripheral intravenous access exposes infants to high rates of clinically minor and serious complications. Despite this, little is known about the interplay of risk factors. The aim of this study was to assess the incidence and evaluate the interactions of risk factors on the occurrence of peripheral intravenous complications in a neonatal population. DESIGN: This was a retrospective observational study. SETTING: The study was performed on the neonatal intensive care unit of the Women's Wellness and Research Center, Hamad Medical Corporation, Qatar, as a single-site study. PARTICIPANTS: This study included 12 978 neonates who required intravenous therapy. OUTCOME MEASUREMENTS: The main outcome was the occurrence of any peripheral intravenous cannulation failure, leading to unplanned removal of the device before completion of the intended intravenous therapy. RESULTS: A mean dwell time of 36±28 hours was recorded in participants with no complications, whereas the mean dwell time was 31±23 hours in participants with an indication for premature removal of the peripheral intravenous catheter (PIVC) (p<0.001, t=11.35). Unplanned removal occurred in 59% of cases; the overall complication rate was 18 per 1000 catheter days. Unmodifiable factors affecting PIVC dwell time include lower birth (HR=0.23, 0.20 to 0.28, p<0.001) and current body weight (HR=1.06, 1.03 to 1.10, p=0.018). Cannulation site (HR=1.23, 1.16 to 1.30, p<0.001), the inserted device (HR=0.89, 0.84 to 0.94, p<0.001) and the indication for intravenous treatment (HR=0.76, 0.73 to 0.79, p<0.001) were modifiable factors. CONCLUSION: Most infants experienced a vascular access-related complication. Given the high complication rate, PIVCs should be used judiciously and thought given prior to their use as to whether alternate means of intravenous access might be more appropriate.

Comparison of ultrasound guidance with palpation and direct visualisation for peripheral vein cannulation in adult patients: a systematic review and meta-analysis.

BACKGROUND: Peripheral vein cannulation is a routine and straightforward invasive procedure, although i.v. access can be difficult to obtain. To increase the success rate of inserting an i.v. catheter, many devices have been proposed, including ultrasonography. The objective of this study was to compare ultrasound guidance with the traditional approach of palpation and direct visualisation for peripehral vein cannulation. The primary outcome was successful peripheral i.v. cannulation. METHODS: Database search was performed on PubMed, Clinical Key, CINAHL, Cochrane Library of Clinical Trials, and Trip Database (from January 2000 to December 2017). Random-effect meta-analysis was performed to determine the pooled odds ratio for success in peripheral i.v. cannulation. RESULTS: After database review and eligibility screening, eight studies were included in the final analysis, with a total of 1660 patients. The success rate in the ultrasound group was 81% (n=855), and was 70% (n=805) in the control group, resulting in a pooled odds ratio for success upon ultrasound-guided peripheral i.v. cannulation of 2.49 (95% confidence interval 1.37-4.52, P=0.003). Furthermore, the ultrasound-guided technique reduced the number of punctures and time needed to achieve i.v. access, and increased the level of patient satisfaction, although it did not result in a decreased number of complications. CONCLUSIONS: Ultrasound guidance increases the success rate of peripheral i.v. cannulation, especially in patients with known or predicted difficult i.v. access.

State of the ART: clinical efficacy and improved quality of life in the public antiretroviral therapy program, Free State province, South Africa.

The South African public-sector antiretroviral treatment (ART) program has yielded promising early results. To extend and reinforce these preliminary findings, we undertook a detailed assessment of the clinical efficacy and outcomes over two years of ART. The primary objective was to assess the clinical outcomes and adverse effects of two years of ART, while identifying the possible effects of baseline health and patient characteristics. A secondary objective was to address the interplay between positive and negative outcomes (clinical benefits versus adverse effects) in terms of the patients' physical and emotional quality of life (QoL). Clinical outcome, baseline characteristics, health status, and physical and emotional QoL scores were determined from clinical files and interviews with 268 patients enrolled in the Free State ART program at three time points (6, 12, and 24 months of ART). Age, sex, education, and baseline health (CD4 cell count and viral load) were all independently associated with the ART outcome in the early stages of treatment, but their impact diminished as the treatment progressed. The number of patients classified as treatment successes increased over the first two years of ART, whereas the proportion of patients experiencing adverse effects diminished. Importantly, our findings show that ART had strong and stable positive effects on physical and emotional QoL. These favorable results demonstrate that a well-managed public-sector ART program can be very successful within a high-HIV-prevalence resource-limited setting. This finding emphasizes the need to adopt treatment scale-up as a key policy priority, while at the same time ensuring that the highest standards of healthcare provision are maintained. Healthcare services should also target vulnerable groups (males, less-educated patients, those with low baseline CD4 cell counts, and high baseline viral loads) who are most likely to experience treatment failure.

Soil suppressiveness to Rhizoctonia solani and microbial diversity.

Rhizoctonia solani anastomosis group 2-2IIIB causes damping-off, black root rot and crown rot in sugar beet (Beta vulgaris). Based on experiences of growers and field experiments, soils can become suppressive to R. solani. The fungus may be present in the soil, but the plant does not show symptoms. Understanding the mechanisms causing soil suppressiveness to R. solani is essential for the development of environmentally friendly control strategies of rhizoctonia root rot in sugar beet. A bioassay that discriminates soils in their level of disease suppressiveness was developed. Results of bioassays were in accordance with field observations. Preliminary results indicate an active role of microbial communities. Our research is focused on the disentanglement of biological mechanisms causing soil suppressiveness to R. solani in sugar beet. Therefore, we are handling a multidisciplinary approach through experimental fields, bioassays, several in vitro techniques and molecular techniques (PCR-DGGE).

Rubella seropositivity in the United States, 1988-1994.

Data obtained in the third National Health and Nutrition Examination Survey (NHANES III), conducted during 1988-1994, were analyzed to determine the epidemiology of rubella seropositivity in the United States, including risk factors for low rubella seropositivity. Serological samples obtained from NHANES III study participants > or =6 years of age were tested for rubella IgG antibodies. "Rubella seropositivity" was defined as serum rubella IgG antibody level > or =10 IU by enzyme immunoassay. Overall, rubella seropositivity rates in the United States were 92% in persons aged 6-11 years, 83% in persons aged 12-19 years, 85% in persons aged 20-29 years, 89% in persons aged 30-39 years, and >or =93% in persons aged > or =40 years. The lowest rate (78%) of any United States birth cohort of the 20th century occurred among persons born from 1970-1974. Eliminating rubella and chronic rubella syndrome in the United States will require international efforts, including vaccination of preschool- and school-age children and all susceptible young adults.

[Critical review of anti-influenza drugs]. / Griepremmers in kritisch perspectief.

Neuraminidase inhibitors such as zanamivir and oseltamivir belong to a new class of antiviral drugs for the treatment and prevention of influenza. As yet however, the therapeutic efficacy of these drugs (shortening of recovery time by approximately one day) has only been demonstrated in healthy adults affected by influenza A, but not in risk groups and in influenza B disease, whereas studies of prophylactic efficacy are still going on. Neither do these drugs impact on viral spread, a public health risk against which the economic advantages of early work resumption have to be weighed. Since flu symptoms can be caused by other germs than the influenza A or B virus, caution in prescribing these drugs seems warranted, also to prevent the development of drug resistance. In addition, when designing therapeutic efficacy trials in risk groups, selecting the rate of secondary complications and death may be more adequate as clinical endpoint than (economically important) duration of illness.

Factors affecting the immunogenicity and potency of tetanus toxoid: implications for the elimination of neonatal and non-neonatal tetanus as public health problems.

An estimated 400,000 deaths occur annually from neonatal tetanus (NT). In 1989 WHO adopted the goal of eliminating NT as a public health problem worldwide. To achieve this, and to control non-neonatal tetanus (non-NT), WHO recommends that newborns be passively protected at birth by the antepartum administration of at least two doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least three doses of diphtheria-tetanus-pertussis (DTP) vaccine. For this strategy to be effective, the TT used must be immunogenic. Potential factors that may affect TT immunogenicity need to be evaluated if NT is to be eliminated and if non-NT is to be controlled. Although data are conflicting, concurrent malarial infection may decrease the immune response to TT; however, malarial chemoprophylaxis may enhance the immune response. Malnutrition does not appear to affect immunogenicity; nevertheless, one study suggests that vitamin A deficiency is associated with an impaired immune response. Although it has been postulated that placental transfer of tetanus antibody is impaired in African women, a survey of the published literature suggests that this is not the case. Freezing TT has been shown to decrease its potency, but its impact on immunogenicity needs more evaluation.

PIP: An estimated 400,000 children die annually due to neonatal tetanus (NT). In 1989, the World Health Organization (WHO) adopted the goal of eliminating NT as a public health problem worldwide. To that end, and in order to control non-neonatal tetanus (non-NT), the WHO recommends that newborn infants be passively protected at birth by the antepartum administration of at least 2 doses of tetanus toxoid (TT) to their mothers and that all children subsequently receive at least 3 doses of diphtheria-tetanus-pertussis (DTP) vaccine. However, the TT employed must be immunogenic in order for the strategy to work. Although the data are conflicting, concurrent malarial infection may decrease the immune response to TT, while malarial chemoprophylaxis may enhance immune response. Malnutrition does not appear to affect immunogenicity, although a study suggests that vitamin A deficiency is associated with an impaired immune response. A survey of the published literature suggests that there is no basis for accepting the hypothesis that placental transfer of tetanus antibody is impaired in African women. Finally, freezing TT has been shown to decrease its potency, but its effect upon immunogenicity remains to be determined.

Sociodemographic, hygienic and nutritional correlates of Helicobacter pylori infection of young Bangladeshi children.

BACKGROUND: By the age of 10 years most children in developing countries have been infected by Helicobacter pylori Identification of clues to modes of transmission of this organism to children, as well as evaluation of the sequelae of childhood infections, constitute important research priorities for developing countries. OBJECTIVES: To evaluate demographic, socioeconomic and hygienic factors associated with acquisition of infection by H. pylori early in childhood among Bangladeshi children ages 2 to 5 years and to assess whether infection by H. pylori was associated with poor nutritional status in these children and in an older group ages 6 to 9 years. METHODS: A random population-based survey of 257 rural Bangladeshi children ages 2 to 5 years and 312 children ages 6 to 9 years. Seropositivity for H. pylori, as manifested by the presence of serum IgG anti-H. pylori antibodies, was correlated with nutritional status of the sampled children and with sociodemographic features and access to clean water and latrine facilities among families of the children. RESULTS: Among children ages 2 to 5 years, the 123 (48%) who were infected by H. pylori were similar to the 134 noninfected children with respect to socioeconomic level, family access to tube well water and family ownership of a latrine. However, families of infected children had more persons per sleeping room in the home (3.8 vs. 3.2, P < 0.05) and were more likely to be Hindu (20% vs. 10%, P < 0.05). Infected children did not differ significantly from noninfected children in Z scores for weight-for-age (-2.66 vs. -2.78), weight-for-height (-1.17 vs. -1.28) or height-for-age (-3.58 vs. -3.56). Analysis of survey children ages 6 to 9 years also revealed similar nutritional indexes among infected vs. noninfected children. CONCLUSIONS: Household crowding and behaviors that differ between Hindus and Muslims, but not lack of access to clean water and latrines, may enhance the transmission of H. pylori to rural Bangladeshi children. Although confirming the high frequency of infections in young Bangladeshi children, our findings do not support the notion that H. pylori is responsible for the high prevalence of malnutrition in this setting.

The effect of L-glutamine on salt and water absorption: a jejunal perfusion study in cholera in humans.

OBJECTIVES: To assess the efficacy of an L-glutamine solution on jejunal salt and water absorption in cholera patients. DESIGN: A randomized double-blind jejunal perfusion study. SETTING: International Centre for Diarrhoeal Disease Research, Bangladesh. PATIENTS: Nineteen adults with acute cholera. INTERVENTIONS: Perfusion of balanced salt solutions alternated with defined glucose salt solution and glutamine glucose salt or alanine glucose salt solutions. MAIN OUTCOME MEASURES: Net jejunal water and sodium secretion. RESULTS: Perfusion of glutamine in the presence of glucose significantly reduced net water secretion (JnetH2O = -2.6 +/- 1.3 ml/h/cm) and also reduced net sodium secretion (JnetNa = -213 +/- 153 mumol/h/cm). Similar results were observed during the perfusion of solutions that contained alanine in addition to glucose (JnetH2O = -4.2 +/- 1.1 ml/h/cm and JnetNa = -444 U +/- 142 mumol/h/cm, respectively) or glucose alone (JnetH2O = -4.3 +/- 1.7 ml/h/cm and JnetNa = -452 +/- 212 mumol/h/cm, respectively). In addition, a higher basal secretion was associated with a greater stimulation of water absorption (F = 17, P < 0.001). CONCLUSION: Glutamine in the presence of glucose significantly reduces net water secretion and also reduces sodium secretion; higher basal secretion is associated with greater water absorption. As glutamine is able to stimulate water absorption to the same degree as glucose and alanine, and because it has the theoretical advantage of providing fuel for the mucosa, the inclusion of glutamine as the sole substrate in oral rehydration solution warrants further study.

Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up.

To determine the protective efficacy (PE) of three doses of oral B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) vaccines against cholera, a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh. During 5 years of follow-up, there were 144 cases of cholera in the BS-WC group (PE = 49%; P < 0.001), 150 in the WC group (PE = 47%; P < 0.001), and 283 in the K12 group. Protection by each vaccine was evident only during the first three years of follow-up; long-term protection of young children was observed only against classical but not El Tor cholera; 3-year protection against both cholera biotypes occurred among older persons, but at a higher level against classical cholera.

Performance and potency of tetanus toxoid: implications for eliminating neonatal tetanus.

Neonatal tetanus (NT) is a major cause of mortality in developing countries, with over 400,000 deaths estimated to occur annually. WHO has adopted the goal of eliminating NT worldwide, and a major strategy for its prevention is the administration of at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas to protect passively their newborns at birth. In certain countries the locally produced TT vaccine has been shown to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was carried out between 1993 and 1995 in 8 of 22 TT-producing countries that also report NT cases, with a more superficial assessment being carried out in the remaining 14 countries. Only 4 of the 22 countries have a functioning national control authority to monitor TT production and vaccine quality. A total of 80 TT lots from 21 manufacturers in 14 of the 22 NT-reporting countries were tested for potency. Of these, 15 lots from eight manufacturers in seven countries had potency values below WHO requirements. TT potency can also be compromised by improper vaccine handling. To eliminate neonatal tetanus worldwide requires assurance that all doses of TT meet WHO production and quality requirements and that the field effectiveness of TT is monitored through systematic NT case investigations and assessment of coverage.

PIP: Neonatal tetanus (NT) causes an estimated 400,000 deaths annually in developing countries. One major way to prevent NT is to administer at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas in order to passively protect their newborns at birth. However, locally-produced TT vaccine in some countries has been found to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was conducted between 1993 and 1995 in 8 of 22 TT-producing countries which also report NT cases. A less exhaustive examination was conducted in the other 14 countries. Among the 22 countries which both report NT cases and produce TT, only Brazil, India, Indonesia, and Mexico have fully functioning national control authorities to monitor TT production and vaccine quality. 80 TT lots from 21 manufacturers in 14 of the 22 countries were tested for potency. 15 lots from 8 manufacturers in 7 countries had potency values below World Health Organization (WHO) requirements. TT potency can also be compromised by improper vaccine handling. If NT is going to be eliminated worldwide, all doses of TT must meet WHO production and quality requirements. Moreover, the field effectiveness of TT must be monitored through systematic NT case investigations and the assessment of coverage.

Impaired immune response to natural infection as a correlate of vaccine failure in a field trial of killed oral cholera vaccines.

In a field trial carried out in 1985 in Matlab, Bangladesh, the authors evaluated whether subjects who developed Vibrio cholerae 01 infections during the first year after earlier receipt of B subunit-killed whole cell (BS-WC) or killed whole cell-only (WC) oral cholera vaccines exhibited deficient serum vibriocidal immune responses to these infections. After severe V. cholerae 01 infections (n = 70) in subjects > 5 years of age, the age group in which both vaccines were efficacious, a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among vaccinees, compared with an 18.6 geometric mean-fold rise in placebo-recipients (p < 0.01). Depressions of serum vibriocidal responses among vaccinees were even more marked after asymptomatic infections (n = 30): a 1.1 geometric mean-fold rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients (p < 0.01). The authors conclude that subjects who failed to be protected by BS-WC and WC, despite being in the age group for which these vaccines were protective, exhibited poor immune responses even to the vigorous stimulus of natural infection. These findings raise the possibility that immune hyporesponsiveness may limit the potential efficacy attainable by cholera vaccines in populations with endemic cholera.

PIP: Natural infections by Vibrio cholerae 01 are known to confer substantial protection against recurrent infections in populations where cholera is endemic. This suggests that it may one day be possible to develop a highly effective oral vaccine against cholera. It is, however, curious that cholera continues to occur into adulthood in populations which have endemic cholera. This phenomenon could be the result of an inability among some individuals in endemic populations to mount suitable immune responses to natural infections. If such immune hyporesponsiveness is truly at work, it may be an important barrier against the development and use of an effective oral cholera vaccine. The authors evaluated whether deficient immune responses to natural infection were associated with the risk of vaccine failure among recipients of killed oral cholera vaccines in a field trial in Bangladesh during 1985. Their findings support the hypothesis that immune hyporesponsiveness, even after the vigorous stimulus of natural infection, may have limited the protection conferred by the vaccines studied in the trial.

Mumps surveillance--United States, 1988-1993.

PROBLEM/CONDITION: CDC monitors the incidence of mumps in the United States through the passive reporting of cases to its National Notifiable Disease Surveillance System (NNDSS). REPORTING PERIOD COVERED: 1988-1993. DESCRIPTION OF SYSTEM: Weekly reports to the NNDSS from 48 states and the District of Columbia were used to calculate incidence rates for mumps. State immunization requirements were obtained from the U.S. Department of Health and Human Services. RESULTS: After the licensure of mumps vaccine in the United States in December 1967 and the subsequent introduction of state immunization laws in an increasing number of states, the reported incidence of mumps decreased substantially. The 1,692 cases of mumps reported for 1993 represent the lowest number of cases ever reported to NNDSS and a 99% decrease from the 152,209 cases reported for 1968. During 1988-1993, most cases occurred in children 5-14 years of age (52%) and in persons > or = 15 years of age (36%). Although the incidence decreased in all age groups, the largest decreases (> 50% reduction in incidence rate per 100,000 population) occurred in persons > or = 10 years of age. Overall, the incidence of mumps was lowest in states that had comprehensive school immunization laws requiring mumps vaccination and highest in states that did not have such requirements. INTERPRETATION: Because of the extensive use of mumps vaccine and the increased number of states that had enacted mumps immunization laws, the number of reported mumps cases decreased further since the marked decline that began during the early 1970s. The earlier shift in incidence from children of school ages to older persons that was noted during 1985-1988 continued until 1992, when the proportion of cases occurring in children of school ages increased and exceeded the proportions occurring in other age groups. ACTIONS TAKEN: All health-care providers are encouraged to a) report mumps cases to their local and state health departments for transmission to NNDSS and b) enact school immunization laws requiring mumps vaccination.

Impact of infection by Helicobacter pylori on the risk and severity of endemic cholera.

To evaluate the relationship between Helicobacter pylori infection and the subsequent risk and severity of endemic Vibrio cholerae O1 diarrhea among rural Bangladeshis, 285 children and adults with cholera (cases) and 881 contemporaneously selected community controls were studied. Cases and controls were contrasted for H. pylori infection, as manifested by serum IgG anti-H. pylori antibodies. Although the overall risk of cholera was not significantly increased among H. pylori-infected subjects, the risk of cholera of life-threatening severity was significantly elevated (relative risk [RR] = 1.61; 95% confidence interval [CI] = 1.07-2.42). A significant increase in the risk of severe cholera was seen in subjects who lacked natural serum vibriocidal antibodies (RR = 2.88; 95% CI = 1.28-6.48) but not in those with such antibodies. Thus, H. pylori infection was associated with a significant increase in the risk of life-threatening cholera, but only among persons lacking natural vibriocidal immunity.

The design and analysis of cholera vaccine trials: recent lessons from Bangladesh.

The recent spread of cholera to Latin America, together with the persistent burden of this disease in Asia and Africa, have stimulated efforts to evaluate new cholera vaccines in field settings. Although the standard experimental paradigm for vaccine field trials is well established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the setting under study. Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable, multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial. They also underscore how the filtering effect of enrolling subjects into a prospective trial can dramatically reduce the available population for study, and can yield a study sample whose expected risk of cholera differs markedly from that for the source population. Finally, the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy, and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups, and in subjects exposed to classical versus El Tor cholera.

PIP: It is important to predict cholera incidence for clinical trials, but it is hard to do so, even in areas where there is a regular endemic pattern. In Matlab, Bangladesh, cholera tends to occur seasonally, right before and after the summer monsoon. Various host facts affect cholera incidence, e.g., insufficient natural immunity and exposure to infected persons. Passive surveillance data in Matlab demonstrate that cholera occurs in a temporo-spatially clustered, multifocal pattern within a community. Ineligibility, refusal to participate, and absenteeism have a strong filtering effect on the population in a field trial. For example, in a field trial of killed oral cholera vaccines in Bangladesh, only 62.285 of the original 124,035 people completed the trial. As a result of nonparticipation, the expected incidence for nonvaccinees was overestimated. The definition of cholera used also determines incidence. For example, if a trial in endemic areas uses the classical definition (watery diarrhea with excretion of cholera vibrios but no copathogens), it would miss those cases with atypical symptoms (e.g., 21% of treated cholera episodes in the oral vaccine trial were clinically atypical or microbiologically mixed). Age related distinctions, ABO blood group, and biotype of the infecting organisms all influence vaccine efficacy. The above issues were considered when designing field trails of killed oral cholera vaccines in Colombia and Peru, but most people in these countries lack preexisting natural immunity, these areas have only E1 for cholera, and it will be very difficult to predict incidence among nonvaccines. This review of epidemiological studies of cholera in Bangladesh, including a large-scale field trial of killed oral cholera vaccines, describes the significance of these considerations.

Immunogenicity of a supplemental dose of oral versus inactivated poliovirus vaccine.

In many developing countries, the immunogenicity of three doses of live, attenuated, oral poliovirus vaccine (OPV) is lower than that in industrialised countries. We evaluated serum neutralising antibody responses in 368 children aged 6 months and 346 children aged 9 months in Côte d'Ivoire who had previously received three doses of OPV at 2, 3, and 4 months of age, and who were then randomised to receive a supplemental dose of OPV or enhanced-potency inactivated poliovirus vaccine (IPV) at the time of measles vaccination. Although both vaccines increased seroconversion to all three poliovirus types, antibody responses were greater in the IPV group. Among children with no detectable antibody at baseline, IPV was 2 to 14 times more likely than OPV to induce seroconversion (type 1, 80% vs 40% at 6 months [p < 0.001] and 81% vs 14% at 9 months [p < 0.001]; type 3, 76% vs 22% at 6 months [p < 0.001], and 67% vs 5% at 9 months [p < 0.001]. Among children with detectable antibody at baseline, IPV was 1.4 to 7 times more likely than OPV to elicit 4-fold or more rises in antibody titre (p < 0.01). Geometric mean titres (GMTs) to all three poliovirus types were also consistently higher among IPV recipients than in OPV recipients when measured 4-6 weeks and 13-17 months after vaccination. Administration of a supplemental dose of IPV or OPV, which requires no additional visits or changes in the existing immunisation schedule, might improve protection against paralytic poliomyelitis in communities with suboptimum seroconversion rates after three doses of OPV.