Recommendations pertaining to the use of viral vaccines: influenza 2006.
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Biomedical subjects
Publications and source records attributed to B D Schoub.
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HIV-1 sequences from two possible transmission cases in South Africa were examined for evidence of genetic linkage. HIV-1-seropositive blood samples were obtained from a donor and recipient within 8 months following a blood transfusion and from a healthcare worker and her patient within 10 months following a needle-stick injury. A 700-bp region in env and 550-bp region in gag were analyzed. All sequences were phylogenetically associated with HIV-1 subtype C, the predominant HIV-1 subtype in South Africa. The nucleotide sequences from the blood transfusion case grouped together significantly with a bootstrap value of 100%. These samples were 98% and 100% identical in the predicted amino acid sequences of env and gag, respectively. In contrast, sequences from the needle-stick case showed only 67% and 80% amino acid identity in env and gag, respectively, and were separated on a phylogenetic tree. Molecular analysis suggested that HIV transmission occurred in the blood transfusion case but not in the case of the needle-stick injury. These data emphasize the need for molecular investigation of epidemiologically linked cases of HIV transmission.
Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in children in both the industrialized and developing world. Most molecular epidemiological studies have, until now, focused on isolates from hospitalized infants in industrialized countries. Limited data have been available with regard to community circulating RSV, especially from Africa. The present study compares RSV isolates from infants attending rural community clinics in the Northern province of South Africa, with isolates from hospitalized infants in Soweto, near Johannesburg, South Africa, during the same period. A multiplex nested polymerase chain reaction was developed for analyzing the clinical specimens, a technique that permits subtyping and nucleotide sequence analysis of the second variable region of the G-protein gene. Community- and hospital-based isolates from young children in South Africa, as well as isolates from Mozambique were compared phylogenetically. One subgroup B community isolate was identified that had a G-protein truncated by approximately 35 amino acids, however, the other community isolates were not significantly different from hospital isolates. Evidence was found that the same RSV genotypes and viruses could cause mild upper respiratory tract infections or lower respiratory tract infections or severe RSV in young infants.
OBJECTIVE: To evaluate the effectiveness of universal vaccination against viral hepatitis B in South Africa among 18-month-old rural children. METHODS: Children were immunized with a course of low-dose (1.5 microg), plasma-derived hepatitis B vaccine at 6, 10 and 14 weeks of age, and blood samples from the children were tested for three hepatitis B markers: hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc. FINDINGS: One year after vaccination, a protective anti-HBs antibody titre of at least 10 IU/l was present in 669/769 (87.0%) of blood serum samples tested. Only 3/756 children (0.4%) were HBsAg positive and a fourth child was anti-HBc positive (HBsAg negative). This is a marked decrease compared to the hepatitis B prevalences reported in previous studies. Among rural migrant mine-workers, for example, HBsAg prevalence was 9.9%, and was 10.1% among children 0-6 years of age in the Eastern Cape Province. CONCLUSION: The low-dose, plasma-derived hepatitis B vaccine, which is affordable to most developing countries, was very successful in controlling endemic hepatitis B infection, where the virus is predominantly spread by horizontal transmission among infants and young children.
OBJECTIVES: To determine the level of immunity to polio in adult personnel at the National Institute for Virology (NIV), South Africa. METHODS: Polio neutralizing antibodies results on 776 NIV staff members tested between 1979 and 1999 and seroresponses in seronegative personnel given a booster vaccination were analysed. RESULTS: 613 of the 776 (79%) personnel had neutralizing polio antibodies to all three types, independent of age, gender, race or job category. Types 1 and 2 antibodies were found in 92% and 94%, respectively, but type 3 was less prevalent at 87%. Of the 93 persons seronegative to one or more types, 13 failed to respond to the first booster vaccination and 8 remained as non-responders after two booster vaccinations. Of the 19 personnel who were bled four days after booster vaccination, 16 (84%) had already developed an antibody response. CONCLUSIONS: Most (79%) adult laboratory personnel retained detectable levels of neutralizing antibodies to polio, independent of age, gender, race or job category, and even in those persons lacking detectable antibodies, most (84%) responded with a secondary immune response. Nevertheless the immunity gap, particularly to type 3, mandates routine screening of personnel potentially exposed to wild-type polio virus and a booster vaccination for seronegatives.
Despite daunting competing health priorities, Africa has made significant progress in polio control. Northern and Southern Africa appear to be polio-free and may shortly be certified as such; however, polio still remains endemic in West and Central Africa and the Horn of Africa. Countries "in difficult circumstancess", wracked by major civil wars, have particularly low routine vaccine coverage, although NIDS have been carried out during negotiated days of tranquillity. AFP surveillance has also improved, although the quality of stool specimens is still far from ideal. There is, nevertheless, an extraordinary political commitment to the eradication campaign. Lessons from the history of polio in the continent need to be heeded in designing end-game strategies. Obstacles on the path to successful eradication are undoubtedly more formidable on the African continent--perhaps the most serious of all are the continuing wars. International political commitment and focussed and empowering developmental aid are urgently needed.
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In 1998 South Africa experienced a major influenza epidemic that was characterized by extensive illness and an unusually early season. The impact of the epidemic was charted by measuring proxy indexes of influenza activity such as school absenteeism and excess mortality in persons older than 65 years. Viruses isolated from patients of all age groups were analyzed both antigenically and at the molecular level to determine the characteristics of the influenza strain responsible for the outbreaks. The study revealed that influenza activity was detected as early as the middle of April and peaked toward the end of May and early June. School absenteeism correlated with a sharp rise in virus isolation during this period. Consumption of influenza-related pharmaceuticals, as well as mortality figures, also corresponded to the increased absenteeism and virus isolation. Characterization of the viruses isolated during 1997 and 1998 showed clearly that the epidemic was caused by the introduction of the A/Sydney/5/97-like H3N2 influenza strain into South Africa in 1998. With no prior exposure to this virus strain, which is antigenically distinct from the viruses that had been present in this country in 1997, the population was highly susceptible, resulting in an early, rapid spread of influenza. This epidemic has highlighted the importance of having an influenza vaccine specifically formulated for the Southern Hemisphere. If the 1998 vaccine had not contained the A/Sydney/5/97 strain, the widespread outbreaks in South Africa would have been far worse in terms of morbidity, mortality, and economic loss. This, in turn, emphasizes the need for increased influenza surveillance and international cooperation.
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The genetic stability of the three Sabin oral poliovaccine (OPV) strains produced on either primary monkey kidney (VK) or Vero cell substrates was compared in vivo and in vitro by measuring the rate at which the bases most strongly associated with attenuation and reversion to neurovirulence (positions 480, 481, and 472 in the 5' non-coding region of Sabin 1, 2 and 3 respectively, and 2034 in VP3 of Sabin 3) reverted during passage of the vaccine strains in the gastrointestinal tract of primary vaccinees and in cell culture. For the in vivo study, the poliovirus excretion patterns of 21 infants receiving OPV produced on either VK or Vero cells were followed for 21 days. No significant differences in either the frequency of excretion or the rate of reversion were observed between the two vaccine groups. The rate of accumulation of revertants during passage in vitro was compared for the three Sabin strains passaged 10 times in either VK or Vero cells. For types 1 and 3, revertants accumulated faster upon passage through VK cells compared with passage through Vero cells. Type 2 appeared to be stable as no revertants were detected in either cell type. Results of this study suggest that the use of Vero as opposed to VK cells as substrate for the manufacture of OPV does not negatively influence the genetic stability of the three Sabin OPV strains in vivo or in vitro.
A seroprevalence study for poliomyelitis was carried out on a sample of sera from a serum bank used for a vitamin A study. Vaccination coverage was satisfactory (80% or more) in five of nine provinces, although a prevalence of antibody to polio of 80% or more was found in all provinces. Serologic immunity (i.e., the prevalence of neutralizing antibodies) exceeded vaccination coverage, suggesting secondary spread of vaccine virus. However, whether or not water was supplied through a piped system was not associated with secondary spread of vaccine virus to nonvaccinated children. Seroprevalence studies are a valuable adjunct to acute flaccid paralysis surveillance, which is the standard surveillance instrument for the poliomyelitis eradication initiative. The use of available and suitable serum banks for seroprevalence investigations is a relatively cheap monitoring option that can yield very valuable information for the eradication initiative.
The analysis of stored sera for retrospective molecular epidemiological studies provides a powerful tool to investigate strain variation in measles viruses that had circulated up to 20 years ago. For this purpose, a rapid and simple method for extraction of RNA from stored sera and cerebrospinal fluids (CSF) was developed. When used on sera and CSFs that have been frozen for as long as 20 years, this method proved to be more efficient than established techniques. The extracted RNA was reverse transcribed into cDNA by using random hexamer primers. The PCR amplification of the 3' terminus of the nucleocapsid gene (N) was divided into two overlapping fragments of 375 and 384 bp length, covering the entire region of interest. This region is thought to have the highest variability within the MV genome and has previously been shown to be suitable for strain characterization. The resulting PCR fragments were sequenced manually by using standard methods without the need of further clean-up steps.
The molecular epidemiology of wild-type 1 polioviruses isolated in South Africa during 2 major poliomyelitis epidemics in the 1980s and during the pre- and inter-epidemic periods was investigated by partial sequence analysis across the VP1/2A junction. Poliovirus-specific primers were used to amplify and subsequently sequence the region of interest. Viruses belonging to different genotypes were found to have been responsible for the 2 outbreaks. The Gazankulu outbreak in 1982 was caused by a poliovirus genotype which was unique to South Africa and which circulated endemically throughout much of the country between 1980 and 1985. Two additional genotypes, imported from the Middle East and West Africa, cocirculated endemically with the South African genotype between 1982 and 1985. The 1988 epidemic in Kwazulu-Natal was attributed to an imported genotype apparently introduced into South Africa in 1985 from countries north of the border. This genotype displaced the 3 genotypes previously in circulation and continued to be transmitted within the country until 1989, when the last confirmed cases of poliomyelitis associated with wild-type viruses were documented. All circulating wild-type poliovirus strains appear to have been eliminated from South Africa.
The genetic relationships between type 1 polioviruses circulating in sub-Saharan Africa during the past decade have been investigated by partial genomic sequencing across the VP1/2A region of the polioviral genome. Sequencing templates were generated by single-step reverse transcription PCR amplification of the viral RNA using poliovirus-specific primers. Seven poliovirus genotypes, circulating in different geographical regions during different periods, were identified. Considerable genetic variation was exhibited by strains within several of these genotypes, indicative of sustained endemic transmission within individual countries. Two genotypes appear to be circulating in Africa at present; one major genotype, which has been in circulation since at least 1980, covers a wide geographical region and includes countries in western, central and southern Africa. Within this genotype are several smaller clusters, possibly representing strains in the process of evolving into new genotypes. The second genotype presently in circulation has been found only in Tanzania and Zambia to date, associated with a relatively small number of cases. Imported genotypes, introduced from the Middle East and the Indian subcontinent, have also recently been in circulation in eastern and central Africa. In South Africa, three genotypes, one unique to the country and the others imported from west Africa and the Middle East, co-circulated endemically between 1980 and 1985. A fourth genotype, introduced from countries to the north, displaced the endemic strains and continued to circulate until 1989. This study has generated a meaningful overview of the endemic circulation and regional transmission of type 1 polioviruses throughout sub-Saharan Africa.
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A heteroduplex mobility assay (HMA) was developed for intratypic differentiation between poliovirus isolates. The assay is based on polymerase chain reaction (PCR) amplification of a 480 base pair fragment which encodes a variable segment of VP1, followed by denaturation and reannealing of the resulting single strands with those from reference Sabin targets. Mismatches between wild-type and Sabin vaccine templates result in the formation of detectable heteroduplexes of reduced electrophoretic mobility. Poliovirus strains confirmed previously as wild-type or vaccine-like by PCR and sequencing were all correctly identified using the HMA. Mixtures of both wild-type and vaccine-like strains in a single isolate could also be detected using this technique. The results of this study demonstrate that heteroduplex analysis is a simple, rapid, and sensitive means for differentiating between vaccine-like and wild-type poliovirus isolates.
Southern Africa may be developing into another poliomyelitis-free zone. Apparent control has been achieved in spite of suboptimal coverage, absence of supplementary strategies, vulnerability to importation and major outbreaks of other waterborne pathogens such as typhoid. A number of serological studies have demonstrated significant susceptibility, especially in rural populations, and studies of three southern African epidemics have shown, in two of them, that epidemics can occur in spite of relatively high levels of serological immunity and vaccine coverage if the burden of virus is sufficiently great. Two studies comparing vaccine coverage to serological immunity have shown that only 78% of fully immunized children in one study and 81% in the other study developed antibodies to all three types of poliomyelitis. In two investigations where vaccine samples were recalled for potency testing from peripheral clinics, almost a half and almost a third, respectively, of vaccine vials had titres below WHO recommended cut-off limits. Major logistical and organizational difficulties in storage and transport of vaccine under cold chain conditions were present in South Africa. These are being rectified and energetic attempts are being made, aided by a strong governmental commitment to improve vaccine coverage and to institute mass immunization campaigns. Nevertheless the need for the development of a more stable OPV for developing and tropical countries still remains a major objective in the global eradication of poliomyelitis.