Background. There are inconsistent published data describing the influence of anaesthetic type during caesarean section (CS), on outcomes of preterm neonates. Objectives. To describe indications and type of anaesthesia in preterm neonates and to describe short-term outcomes, comparing spinal anaesthesia (SA) to general anaesthesia (GA). Methods. Data were collected retrospectively on preterm babies born at 28 – 35 weeks' gestation by CS, between 1 January and 30 Sep 2014 at Groote Schuur Hospital, Cape Town, South Africa. Babies with missing data were excluded. The largest group of babies with similar indications for delivery were identified from the theatre register. Baseline characteristics and short-term outcomes for this group were extracted from an existing prospective data base, and compared between those delivered under SA and GA. Results. Data were available for 226 deliveries, having excluded 23 with incomplete data. Most babies (75%) were delivered under SA. The most common indication for CS was ‘cardiotocograph abnormalities,' in 139 deliveries. Within this group, SA was more frequent (81.7% vs. 12.9%) while GA was associated with lower Apgar scores (p < 0.001) and more intubation at birth (p = 0.004). There was no difference in mortality when comparing SA with GA. Conclusion. Our data suggest a sedative effect of maternal GA on preterm babies delivered by CS, and the need for staff with advanced resuscitation skills. This study provides novel baseline data in our setting, but these data need to be validated in a prospective study.

The availability of an effective vaccine against Bordetella pertussis substantially reduced the morbidity and mortality from pertussis, however, in the last decade there appears to have been a substantial increase in pertussis cases as reported mainly in high income countries. Although it is believed that the greatest burden of pertussis, including deaths, is in low- and middle-income countries (LMICs), there seem to be little data available to back this up. This thesis set out to find data that will give some insight into the burden of pertussis in a low- and middle-income setting in infants and children with severe lower respiratory tract infection (LRTI). Given the paucity of data in LMICs, the thesis starts by systematically searching for existing data that will give some indication of the possible extent of the pertussis problem in these countries. Secondly, a prospective study was conducted at a children's hospital. As hospital admission is a marker of severe disease, these children were targeted as the appropriate population in which to meaningfully conduct a primary study on the burden of pertussis. In addition to quantifying the burden by describing the prevalence of confirmed pertussis in this group of children, the study set out to look for potential factors that may be associated with increased risk of pertussis. LRTI are now commonly known to be associated with identification of multiple organisms in respiratory samples, this study aimed to also look at organisms that are detected with Bordetella pertussis; and investigate whether this association was in any way associated with severe disease or negative outcomes. Finally, as data has been emerging that in the context of immunisation, the clinical presentation of pertussis may no longer be following a classical pattern, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. 2 Chapter 1 gives a background that justifies the undertaking of this study as well as give a summary of the methods used to answer the question of the thesis. The chapter also gives an indication of the structure that the thesis follows. In chapter 2 a systematic review quantifies the burden of pertussis in LMICs using the best available data. In chapter 3 the burden of pertussis due to the two organisms known to cause the disease, Bordetella pertussis and Bordetella parapertussis, is described in some detail. In both this chapter and the earlier mentioned systematic review (chapter 2), the burden of pertussis is stratified by subgroups to identify potential risk factors. The issue of risk is formally and specifically taken up in the chapter that follows (chapter 4) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 5 and 6) deal respectively with the conundrum of finding other respiratory organism in the same specimen with Bordetella pertussis and failure to find useful clinical criteria that can help with improved diagnosis of pertussis, specifically in children presenting with acute severe lower respiratory tract infection. While there is no established pattern noted between pertussis and most organisms, a few give signals of being independently associated with Bordetella pertussis even if the clinical relevance is not clear at the moment. In the final chapter of the thesis (chapter 7) I conclude the thesis by making an argument that although there are still knowledge gaps, the thesis gives a clear indication that pertussis remains a serious problem in LMICs especially for some groups that show increased risk of the disease or its severe consequences.

Lesotho, like many other developing countries, has a high incidence of maternal deaths. Minimal research has however been undertaken to establish the actual maternal mortality rate. The result has been a very wide gap between the officially quoted figure (282/100,000 live births) and the various estimates that have been made over the years. It was only in 1997 that a survey based on active case finding revealed a maternal mortality rate of738/100,000 live births. The researchers noted that not all cases of maternal deaths that occurred during the survey period might have been traced. The figure was however an eye opener to the magnitude of the problem in Lesotho. One of the main limitations of the 1997 survey was that no attempt was made to establish the causes of the documented maternal deaths. This was the motivation behind the current research.

The subject of this research is a basic demographic and health status survey. The location of the study is an informal settlement within the Municipality of Knysna, a town on the Southern Cape coast of South Africa with a population of approximately 40 000. Maps in Appendix 1 and 2 show the Western Cape and the study area respectively. The delivery of health services in the area has historically been fragmented, with the private sector and the provincial hospital providing curative services and the Municipality taking responsibility for environmental and personal preventive care such as immunisation and family planning. As a consequence of fragmented health care delivery, health information systems and planning have not been geographically integrated. The philosophy of a cohesive, well planned and equitable service provided to all residents of a district is dependent on adequate information for planning. It is hoped that this study will inform such a planning process.

Background: Effective workforce planning requires stakeholders to agree about the desired roles and contributions of advanced and specialist nurses across different tiers of service delivery. Role descriptions can help to reduce role confusion and inform workforce planning if stakeholders use them to establish a shared contextual basis for defining roles within their health service or system. There is a scarcity of rigorously developed role descriptions worldwide, especially role descriptions accurately reflecting the work of advanced and specialist nurses in Africa. Aim: Malawi is one of many African countries investing in establishing a specialist children's nursing workforce as part of globally advocated strategies to improve child health. This study aimed to develop a replicable process to assist stakeholders with specialist nursing workforce planning, informed by understanding the roles and contributions of children's nurses in the context of Malawi's health system. Methods: This study used a multiple methods approach with four phases. Design principles of stakeholder engaged research were incorporated into all research activities, which included: 1) a systematic scoping review to inform stakeholder identification; 2) a situational analysis; and 3) focus groups and interviews with 41 children's nurses in Malawi about their roles. Following qualitative content analysis of interview and focus group data, 4) concept mapping was used to integrate characteristics of the roles of children's nurses in Malawi and published role descriptions of other African specialist and advanced nursing roles with global frameworks for advanced nursing roles. Results: The study generated a framework for systematic identification of nursing HRH stakeholders; a situational analysis; and richly descriptive accounts of the roles of children's nurses in Malawi. The major product of the study was a flexible framework proposing four role domains and associated categories of activity for specialist and advanced practice children's nurses in Malawi, also applicable to other specialisations and other African health systems. Conclusions: The flexible framework is a distinctive response to the needs of African health systems. Advanced and specialist nurses in Africa are establishing their newly introduced roles into health systems in transition, within challenged and challenging practice contexts which demand high levels of adaptability. The framework is positioned to form part of a replicable process for stakeholder engaged nursing workforce planning. It is hoped that it will assist nurses and other stakeholders to manage the development of advanced and specialist roles at the levels of individual nurses, institutions and health systems.

Background Since 2010, adult studies and clinical concerns about stavudine (d4T) toxicity had led to the phasing out of d4T from many antiretroviral treatment (ART) guidelines globally with substitution by abacavir. Recent studies, within Southern Africa, however have shown poorer virological suppression with abacavir (ABC) compared to d4T at their respective centres. Methods A retrospective study of HIV-positive children, who had been initiated on ART from 2005 to 2017, was conducted at an ART unit at New Somerset hospital, Western Cape, South Africa. Data was extracted from clinical notes and electronic medical records and virological suppression reviewed in those started on ABC and d4T based regimes. Results A total of 672 children were included in the study with a median age of 8.9 months (interquartile range (IQR) 4.1- 24.1 months) in the d4T based group and 11 months (IQR 3.5 - 29.9 months) in the ABC group. 64 of the 437 patients in the d4T containing group were transferred out, 15 reported to have died, and 49 were lost to follow up within the first 6months on treatment. Of the 181 ABC containing regimen group, 1 was transferred out to another care facility, 1 reported death within 6months of treatment and 2 children were lost to follow up. There was a noted increased risk of being virologically unsuppressed at 6months while taking ABC containing regimen compared to a d4T containing regimen. . The relative risk of being virologically unsuppressed at 6 months while taking abacavir/lopinavir (LPV/r) was 1.39 (95% confidence interval 1.03 to 1.88, p=0.04) compared to stavudine/LPV/r. The relative risk of being virologically unsuppressed at 6 months while taking abacavir/efavirenz (EFV) was 1.82 (95% confidence interval 0.98 to 3.37, p=0.054) compared to stavudine/EFV. Conclusion Our analysis again raises concerns about virological suppression in the abacavir era of paediatric ART, compared to the previous stavudine era, particularly in combination with LPV/r in the younger, more vulnerable children. Whether this is because of intrinsic properties of the different medications or is a marker of the evolving complexity of the South African ART rollout, may never be resolved. However, this is of concern as abacavir and LPV/r appear to be entrenched as first-line paediatric ART in a setting where attrition is high, many children are lost to follow up and virologic surveillance is not always optimal. Clinicians need to optimize retention strategies, especially of young infants, to ensure that children are retained in care, have viral load testing timeously, so that those virologically unsuppressed can be detected and treated early and appropriately.

Includes bibliographical references / Rheumatic Heart Disease (RHD) is a leading cause of heart disease in children and young adults in the developing world, with significant associated morbidity and mortality. Early secondary prophylaxis may retard the deleterious progression from its antecedent, acute rheumatic fever to permanent heart valve damage, and thus several echocardiographic screening programmes to detect asymptomatic RHD and institute early prophylaxis have been conducted. While effective interventions are available for ameliorating the effects of RHD, research on their use in different settings is scant. Key questions remain regarding the natural history of asymptomatic RHD and the optimal method for early detection. In addition, there is a lack of contemporary estimates of mortality and morbidity among the symptomatic population in the developing world. The primary purpose of the thesis was to determine the outcomes of asymptomatic and symptomatic RHD. More specifically, I sought to quantify the incidence, prevalence and outcomes of RHD in South Africa over the past two decades, determine the natural history of asymptomatic RHD and validate a focused protocol for screening in schoolchildren from Cape Town. In addition, I determined the baseline characteristics, prevalent sequelae and gaps in evidence-based implementation in children and adults from14 developing countries. Finally, I investigated the independent predictors for mortality and morbidity of RHD over a two-year period in patients from Cape Town, South Africa. My thesis has five key findings. Firstly, a systematic review of the literature showed that the incidence and prevalence of RHD over the past two decades in South Africa remains high, although there is evidence of falling cause-specific mortality at a population level. Secondly, asymptomatic RHD has a variable natural history that ranges from regression to a normal state, to persistence of disease, and progression to symptomatic RHD. Thirdly, a focused hand-held echocardiography protocol shows promising levels of sensitivity and specificity for detecting subclinical RHD. Fourthly, the baseline data from the global rheumatic heart disease registry demonstrates significant gaps in the implementation of medical and surgical interventions of proven effectiveness in low- and middle-income countries. Finally, the annual mortality rate for children and adults with RHD in Cape Town over a two-year period is 4.1%with cardiovascular events occurring at a rate of 0.18 events per patient per year. The findings encapsulated in this thesis have important implications for policy, practice and research related to the management of asymptomatic and symptomatic RHD in the world.

Vitamin A has well recognised benefits for the reduction in severity of diarrhoeal episodes but the impact of therapeutic doses given during diarrhoea on the biochemical and clinical outcomes is less clear. In this study these potential therapeutic benefits were investigated to establish the optimum time for vitamin A supplementation to improve vitamin A status. Establishing the optimum time for vitamin A supplementation during an infectious stage would improve cost effectiveness and clinical benefit. Young children (174) between the ages of 3 and 60 months with severe diarrhoea were randomised in a double - blinded placebo controlled trial into one of 2 groups. The 1 st group received 60 mg of retinol as retinyl palmitate on admission during the acute diarrhoeal stage. The 2nd group received the same dose of vitamin A once symptoms had resolved, usually between 3 - 7 days. At each of these two time points, children not receiving vitamin A were given an identical placebo dose. Baseline (day 0) and day 3 serum samples were collected for vitamin A, retinol binding protein (RBP) and other biochemical markers. At four and eight weeks after discharge both morbidity and weight gain were recorded. The modified dose response test (MRDR) was conducted at the eight - week follow - up to estimate vitamin A liver stores. Initially, most of the children presented with watery diarrhoea and dehydration and were clinically very ill. At day 3 plasma retinol concentrations improved in both groups viz. from 0.57umol/L to 0.97umol/L in the 1st group and from 0.49umol/L to 0.90umol/L in the 2nd group. Similar improvements were found in retinol binding protein viz. 21.28 mg/L to 31.06 mg/L in the 1st group and 17.05 mg/L to 24.80 mg/L in the 2nd group. At 8 weeks there was also no significant difference between the two groups either for serum retinol (0.69umol/L and 0.73umol/L respectively) nor for MRDR ratios (0.036 and 0.049 respectively). The MRDR results at 8 weeks indicated that these children did not have depleted vitamin A liver stores and that the low serum retinol levels seen at baseline were probably due to the acute phase response during an infectious episode. The results of these analyses showed no significant difference between the two treatment groups thus indicating that there was no benefit to giving vitamin A on recovery from an infectious episode instead of on admission, as is currently practised. / Thesis (M.Med.Sc.)-University of Natal, Durban, 2001.

BACKGROUND Sub-saharan Africa remains to date at the forefront of the HIV/AIDS epidemic. Despite breastfeeding being a significant mode of postnatal HIV transmission it remains the main nutritional source and pillar of child survival for the majority of infants born in Africa. It is therefore, not surprising that considerable research has centred on making breastfeeding safer in terms of HIV transmission. The flash heat treatment method (HTEBM) provides a unique opportunity to safely breastfeed infants but prevent mother-to-child transmission of HIV. Cytotoxic T lymphocyte (CTL) responses have been well documented in HIVinfected adults and children. However, there is a lack of literature on CTL responses in HIV exposed low birth weight infants. This pilot study attempted to examine the association of early neonatal feeding on the clinical outcomes and CTL responses in HIV exposed low birth weight infants. METHODS Seventy-seven patients that fulfilled inclusion and exclusion criteria were enrolled. The clinical outcomes of these patients were evaluated over a 9 month period. Fifty-five of these patients were also investigated for cytotoxic T lymphocyte (CTL) responses by means of the IFNγ ELISpot (megamatrix and confirmation) assays at the 6 weeks, 3, 6,and 9 months follow-up. RESULTS Two HIV-1 infected infants generated a CTL response at a single time point using the ELISPOT matrix screening assay. These responses could not be confirmed and were undetectable at any of the consecutive visits. At the time of detection of responses the infants were fed unheated breastmilk. HIV-1 exposed uninfected infants were unable to elicit a HIV-1-specific CTL response irrespective of feed. With regards to clinical outcomes, infants born o HIV infected mothers with a CD4 count < 500cells/μl were 2x more likely to acquire other infections at birth compared to those infants born to HIV infected mothers with a CD4 count >500cells/μl. Also, infants born to HIV infected mothers with advanced disease (CD4 count 0-200 cells/μl) had a lower birth weight compared to infants born to HIV-1 infected mothers with a CD4 count > 350 cells/μl. We also investigated the feasibility of the flash heat treatment method at birth. While inhospital, 38 HIV-1 infected women fed their infants HTEBM after receiving counseling and support from the nursing staff at the King Edward VIII hospital. The numbers decreased rapidly post hospital discharge, mainly due to mixed feeding. DISCUSSION In conclusion we have shown that it is feasible for HIV infected mothers to heat treat their expressed breastmilk during hospital admission. Furthermore, we were able to demonstrate in this small cohort of patients that the clinical outcomes and growth parameters of infants fed HTEBM were similar to that of infants fed either formula or unheated breastmilk. We were unable to demonstrate HIV-specific responses in the infected infants or the uninfected infants who had been exposed to heat inactivated virus in HTEBM. Our findings indicate that this pilot study was limited in its ability to detect CTL responses in HIV exposed low birth weight infants and further studies are warranted. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2011.

Conventional pertussis vaccine prepared from killed whole cell B. pertussis organisms has been in widespread use since the early 1950's. Despite marked reductions in the incidence of pertussis, the use of the vaccine has caused concern because of questions of significant adverse reactions. Whooping cough is not notifiable in South Africa, and there is consequently a paucity of hard data on efficacy; in addition few cases are proven. Incidence, prevalence, severity and transmission of the disease hence remain a matter of conjecture. In order to provide background information and determine baseline data for undertaking further studies, available clinical and epidemiological data on whooping cough (pertussis) in South Africa was collated. It was intended to compare the pattern of disease seen in this country with that known in other parts of the world. Clinical and epidemiological findings from 1525 whooping cough admissions (diagnosed on the basis of clinical criteria) obtained from 6 major infectious disease hospitals around the country for the period 1980-1987/1988 are reported. The data from Durban were available in some detail. Incidence, morbidity and mortality of the disease in South Africa, as elsewhere, was higher in infancy. Infants and young children were predominantly affected, with 31.3% of cases under 12 months of age and 7.2% less than 2 months. Mortality was disproportionately higher in infancy; 53 .2% of deaths were in those younger than 12 months of age. There was a slight female preponderance, both in respect of prevalence and mortality. Patients were admitted with pertussis throughout the year, although there was a peak during the winter months (May to October). The typical whoop accompanied the cough in 55.6% of patients . A raised white cell count was recorded in 66% of patients. The most commonly detected The average duration of hospital stay was between 1 0-13 days. Of those with vaccination records, 26% were unvaccinated, 44% had 1 or 2 doses, and 27% had been fully vaccinated with a whole-cell pertussis vaccine combined with diphtheria and tetanus toxoids. The picture, incomplete though it is, reveals a pattern of pertussis similar to that described in other developing countries. The study reveals huge gaps in our knowledge of this subject in South Africa. More research needs to be done, particularly with respect to improved diagnosis, prevention and treatment; further pertussis should be made a notifiable disease in South Africa. The whole-cell pertussis vaccine currently used in South Africa has not been adequately evaluated for post-vaccination events and immunogenicity. The development of new purified component pertussis vaccines, which appear to be safer than conventional whole-cell preparations and of equal or almost equal efficacy (although optimal vaccine composition remains to be defined), requires that the concept of early vaccination with this vaccine compared with conventional whole-cell vaccine be examined in order to optimise the immune response to these vaccines in infants; more especially since neonates do not appear to benefit from passive immunity. Acellular pertussis vaccine has not been evaluated previously in neonates. In order to address the problem of high morbidity and mortality from pertussis in early infancy; and the incorporation of the vaccine into routine vaccination schedules, a phase 11 trial of acellular and whole-cell vaccines was undertaken in very young infants. The effect of neonatal vaccination with acellular pertussis vaccine on subsequent immunity; and the immunogenicity and shortterm safety and reactogenicity of routine primary vaccination with acellular vaccine compared with conventional whole-cell preparations was investigated. Three hundred and forty-five healthy, full-term African babies were, enrolled in the study at birth; 58% of whom were successfully followed for 9 months. Infants were assigned to 1 of 3 vaccine groups in sequence at birth and received either acellular or whole-cell pertussis vaccine , combined with 0 and T (A-OTP or W-OTP) at 2, 4 and 6 months of age. Groups I and 11 received A-OTP and Group III W-OTP. In addition, at birth, Group I received an additional dose of A-OTP and Group 11, a saline placebo injection. No unvaccinated controls were studied for ethical reasons. Serologic IgG responses to 3 major protective antigens of B. pertussis, filamentous haemagglutinin (FHA), pertussis toxin (PT) and fimbrial agglutinogens 2,3 (AGG2,3), were measured by ELlSA in sera obtained at birth, and before vaccination at 2, 4 and 6 months and at 9 months of age. The incidence and nature of post-vaccination events were recorded for 14 days after each dose. A-OTP induced serum IgG responses to PT and FHA comparable with those reported in other studies, with peak PT titres occurring at 6 months of age after 2 doses in babies vaccinated according to the routine schedule (Group 11). Surprisingly, response to W-OTP was found merely to restore levels of antibody to PT and FHA to those found in cord blood after 3 doses of vaccine, which questions the immunogenicity of the South African product. Four doses of AOTP (Group I) did not produce a better antibody response than the 3-dose schedule. Incidence of all post-vaccination events to both acellular and whole-cell vaccines was low (85.96/1000 doses, 136.36/1000 doses and 76.30/1000 doses in Groups I, 11 and III respectively). Minor symptoms were more common in recipients of A-OTP, although no significant differences in rates were demonstrated. Neurologic post-vaccination events (without sequelae) occurred more frequently hi recipients of W-OTP. No infant vaccinated with A-OTP from 2 months of age (Group 11) experienced a neurologic symptom. The risks of major post-vaccination events cannot however be fully quantified In a study of this small size and diseases. A-DTP vaccination commencing at birth produced final antibody titres to PT and FHA which were superior to those of South African whole-cell vaccine but were considerably lower than when the vaccine was incorporated into routine schedules commencing at 2 months of age. The study findings suggest that acellular pertussis vaccines, whether given from birth or from the age of 2 months, appeared safer and produced a better serologic response than the South African whole-cell product which may have impaired immunogenicity. During the course of the above study, 11 full-term infants with pertussis infection (10 subclinical) were retrospectively diagnosed on the basis of ser~logic evidence. Of the infants with subclinical disease, all 10 had a ~ 4-fold rise in at least 2 different pertussis IgG antibodies and nine had ~ 4-fold rise in all 3 IgG antibodies measured. Seven infants had raised IgA antibodies to PT and FHA and 4 infants had raised IgA antibodies to AGG2,3. Subclinical infection provoked antibody production to multiple antigens to differing degrees. The role of various factors which may have contributed to asymptomatic infection were analysed, viz - household contacts; type of antibody response (clinical vs. subclinical; vaccinated vs. subclinical); maternally acquired antibody levels; vaccination status (number of vaccine doses received); age and gender; and nutritional status. SpeCial features of the study which require emphasis are: pertussis remained subclinical in unvaccinated babies (most of the subjects were unvaccinated). Subclinical infection followed incomplete primary vaccination with either acellular or whole-cell vaccines commencing at 2 months of age. Subjects were 8 months of age or younger and only 1 had completed primary vaccination. Other infections of infancy were commonly detected; 4 infants had upper Likelihood of subclinical infection was related to significantly lower levels of maternallyacquired pertussis IgG-AGG2,3 antibodies but not associated with infants' nutritional status. Subclinical pertussis is described in very young African babies at an age when the disease is most severe, and therefore has implications for infant morbidity and mortality; it is also relevant to disease surveillance and vaccine-efficacy studies . Some perinatal factors influencing vaccination were also explored . In this context we looked at: i. The acquisition of maternal antibodies to B. pertussis in paired mother-infant sera from both well -nourished and SGA full-term and pre-term infants, and infants who subsequently developed pertussis infection, and effect of these maternally-acquired antibodies on subsequent antibody responses to acellular pertussis vaccine administered soon after birth, and to acellular and whole-cell vaccines administered from the age of 2 months. if. The acquisition of maternal antibodies to diphtheria and tetanus (OT) in paired motherinfant sera from full-term and pre-term infants, and the effect of these maternallyacquired antibodies on serologic responses to neonatal OT vaccination followed by whole-cell OTP vaccination at 2, 4 and 6 months. Maternal antibodies were measured since little is known about materno-fetal transfer of pertussis antibodies, especially in African countries where inhibition of placental transfer might occur for a variety of reasons. Furthermore, the effect of peri-natal malnutrition and prematurity on transplacental transfer of diphtheria, tetanus and pertussis antibodies has not been conclusively established in these areas. sera with levels in the latter frequently being higher, Indicating active transplacental transfer of antibodies. The significant pertussis antibody levels in maternal sera were unlikely to be due to the currently used South African whole-cell vaccine (given the poor antibody response to PT and FHA shown in this study). It is assumed that the presence of these antibodies are the end result of natural infection and therefore that pertussis is widespread in the African community. Maternal and cord IgG-PT and AGG2,3 titres were significantly lower (p <0.05) and maternal IgG-FHA marginally lower (p ... O.05) in SGA infants compared to cohorts, although placental transfer was equally efficient in both groups~ This study has demonstrated that the high titres of maternally derived circulating B. pertussis antibodies do not have an inhibitory effect on the subsequent serologic response to acellular vaccine administered in early infancy (2 months) or with the first dose given soon after birth. Protective levels of diphtheria and tetanus antibodies were detected in 100% and 76% of cord sera in pre-term infants and in 85% and 67% of cord sera in full-term infants. Although the number of infants studied was too small to make a definite comment, there did not appear to be 'tolerance' due to neonatal diphtheria-tetanus vaccination of pre-term infants, or to high levels of maternally-acquired antibody. During analysis of the data from the phase 11 study of acellular pertussis vacclnes, 25 infants with protein-energy-malnutritlon (PEM) were detected on the basis of anthropometric indices. Seventeen infants were smaIJ-for-gestatlonal-age (SGA). of whom 9 developed PEM by the age of 9 months. Eight other infants developed post-natal PEM before the completion of the primary vaccination course. and extent of immunological impairment, if any, on the serologic responses to acellular vaccine and to conventional whole-cell OTP in SGA infants, and in infants who developed PEM before the completion of the primary vaccination course. The following indices were evaluated in malnourished infants; (i) anthropometric indices of nutritional status, (ii) intercurrent illnesses including pertussis infection, (iii) post-vaccination events, (iv) serologic responses to vaccination. Results were compared with those obtained in well-nourished (WN) age- and vaccine-matched cohorts. Overall, peak titres and seroconversion data of all 3 antibodies were not significantly different in malnourished infants though final anti-AGG2,3 titres (at 9 months of age) in Group III were significantly lower (p = 0.035). Although peak and final PT and FHA antibody titres in many SGA and malnourished infants were lower than in WN infants and peak responses were attained at a later age, malnutrition did not significantly affect the response to A-OTP. Peak and final AGG2,3 antibody titres were similar in SGA, malnourished and WN infants. Overall malnourished infants responded no less well to pertussis vaccination than did other vaccinees. Incidence of minor local and systemic post-vaccination symptoms was not significantly different in PEM and WN groups although induration at injection site and irritability were more frequently reported in the latter. No major neurologic post-vaccination symptoms to either vaccine were reported in SGA infants or infants with PEM at the time of vaccination. No significant differences was noted in the incidence of major symptoms in PEM as compared with WN infants. One male infant (Group I) who was malnourished at birth and who had been given 2 doses of AOTP, developed clinical signs of pertussis infection between 2 and 4 months of age. Pertussis antibody levels immediately prior to infection were not significantly different from those of un infected age-matched cohorts. The percentage of infants afflicted with common childhood illnesses were similar in PEM and WN groups (46 vs. 43.2%) although the former group incurred significantly more illnesses at an earlier age' (s6 months) (p=O.05, chi square). These findings, albeit preliminary given the small numbers of subjects studied, suggest that acellular pertussis vaccine may be incorporated into routine vaccination schedules followed in developing countries with the expectation that adequate antibody responses will be provoked in SGA infants and in infants who develop post-natal PEM and that the incidence of vaccinerelated adverse effects will be no higher than in WN infants. Further and more extensive studies are indicated before the use of acellular pertussis vaccines can be recommended for routine primary vaccination of infants in preference to whole-cell preparations in developing countries. / Thesis (Ph.D.)-University of Natal, Durban, 1991.