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BACKGROUND: Trigeminal trophic syndrome is a rare cranial and facial condition caused by damage to the central or peripheral branches of the trigeminal nerve. This syndrome consists of a triad of anesthesia, paresthesia, and crescent-shaped facial ulcer involving the ala nasi and sometimes extending to the upper lip. Although previous screening for human immunodeficiency virus in some patients with trigeminal trophic syndrome was negative, we present a unique case of trigeminal trophic syndrome who tested positive for human immunodeficiency virus with eye complications. CASE PRESENTATION: We present a rare case of trigeminal trophic syndrome in a 44-year-old Black African woman who tested positive for human immunodeficiency virus. She presented with a 6-week history of progressive, persistent, and painless left sided facial and scalp ulcerations that started as small skin erosion. Diagnosis of trigeminal trophic syndrome was made on clinical grounds based on the triad of anesthesia, paresthesia, and unilateral crescent-shaped ulcer in the trigeminal dermatome and her past medical history. The ulcer healed completely after counseling and pharmacological therapy, but she later developed left periorbital cellulitis and left upper eyelid full-thickness defect. CONCLUSION: This is by far the first documented case of trigeminal trophic syndrome with a positive human immunodeficiency virus test. Testing for human immunodeficiency virus in patients with trigeminal trophic syndrome is necessary as this can help improve clinical management and treatment outcomes. Seeking the services of specialists remotely in resource constraint settings is beneficial for managing complications associated with trigeminal trophic syndrome.
Subject(s)
HIV Infections , Humans , Female , Adult , HIV Infections/complications , Trigeminal Nerve Diseases/diagnosis , Cellulitis/diagnosis , Skin Ulcer/etiology , Skin Ulcer/virology , Paresthesia/etiology , Syndrome , Eyelid Diseases/etiology , Eyelid Diseases/diagnosisABSTRACT
BACKGROUND: The Community-based Health Planning and Services (CHPS) initiative plays a key role in delivering maternal and child health nutrition services in Ghana. This study explored bottle necks hindering the delivery of maternal and child nutrition services at CHPS zones and searched for strategies to address them from the perspective of community health officers in rural Northern Ghana. METHODS: An exploratory qualitative cross-sectional study design using key informant interviews involving the municipal nutrition officer and Community Health Officers (CHOs) from eleven CHPS zones was carried out in April 2019. Manual data analysis was done using the framework analysis approach in qualitative data analysis for applied policy research. RESULTS: This study identified challenges of maternal and child nutrition services in the Jirapa municipality to be municipal health directorate and CHPS zone based in nature. Municipal health directorate based challenges were inadequate logistics/medicines; lack of staff training; lack of supervision/monitoring; and inadequate financial support/motivation/incentives. CHPS zone based challenges were lack of planning activities by staff; inadequate home visits; lack of commitment by staff; and lack of community meetings/engagements. Proposed strategies to address municipal health directorate based challenges included adequate provision of logistics/medicines; frequent training of staff in maternal and child nutrition related issues; frequent supervision/monitoring activities from the municipal health directorate; and providing financial support/motivation/incentives at the CHPS zones. Proposed strategies to address CHPS zone based challenges were planning of activities; improved home visits; increased commitment towards delivering maternal and child nutrition services; and frequent community meetings/engagements. CONCLUSION: In order to improve maternal and child nutrition services at CHPS zones, there is the need to address certain systemic challenges at both the municipal or district health directorate and CHPS zones levels of the primary health care system. It is recommended that, the Municipal Health Directorate; the Municipal Health Management Team; the Municipal Assembly and all relevant stakeholders involved in improving maternal and child nutrition services at the community level, actively engage CHOs to help address the systemic challenges.
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BACKGROUND: Despite several efforts at addressing the barriers to adherence to the WHO-supported test, treat and track (T3) malaria case management guideline in Ghana, adherence remains a challenge. This study explored the challenges of prescribers regarding adherence to the T3 guideline. METHODS: This was an explorative study using key informant interviews amongst prescribers comprising medical doctors, physician assistants, nurses and a health extension worker from 16 health facilities in six districts in Ghana. The data was analysed using Nvivo 10 and organized into thematic areas. RESULTS: Prescribers lauded the guideline on testing and treatment as it ensures the quality of malaria case management, but irregular supply of malaria rapid diagnostic test kits (RDT), mistrust of laboratory tests, and the reluctance of prescribers to change from presumptive treatment were key barriers to testing. Patients with malaria test negative results if not treated, revisiting the facility with severe malaria, the experience of prescribers, lack of regular training and supervision for old and new staff and the inability of prescribers to investigate non-malaria fever hindered adherence to results-based treatment. CONCLUSION: As malaria remains a significant cause of morbidity and mortality in Ghana, this study provides insights on gaps in adherence to the testing and treatment of malaria. While the diagnostic capacity for malaria case management is a challenge, the lack of training resulting in the inability of some prescribers to investigate non-malaria fever hinders adherence to the malaria case management guideline. Therefore, there is a need to train new prescribers, laboratory personnel, and other staff involved in malaria diagnosis and treatment on the malaria case management guideline before they assume duty. Equipping laboratory personnel and prescribers with the knowledge to investigate non-malaria fevers could improve adherence to the guideline for improved patient care.
Subject(s)
Antimalarials , Malaria , Physicians , Humans , Case Management , Ghana , Malaria/diagnosis , Malaria/drug therapy , Health Facilities , Guideline Adherence , Antimalarials/therapeutic useABSTRACT
Ghana is positioned to become the first country in sub-Saharan Africa to implement universal health coverage based on nationwide expansion of geographic access through the Community-based Health Planning and Services initiative. This achievement is the outcome of 3 decades of implementation research that health authorities have used for guiding the development of its primary health care program. This implementation research process has comprised Ghana's official endorsement of the 1978 Alma Ata Declaration, leading to the institutionalization of evidence relevant to the strategic design of primary health care and national health insurance policies and services. Rather than relying solely upon the dissemination of project results, Ghana has embraced a continuous and systemic process of knowledge capture, curation, and utilization of evidence in expanding geographic access by a massive expansion in the number of community health service points that has taken decades. A multisectoral approach has been pursued that has involved the creation of systematic partnerships that included all levels of the political system, local development officials, community groups and social networks, multiple university-based disciplines, external development partners, and donors. However, efforts to achieve high levels of financial access through the roll-out of the National Health Insurance Scheme have proceeded at a less consistent pace and been fraught with many challenges. As a result, financial access has been less comprehensive than geographical access despite sequential reforms having been made to both programs. The legacy of activities and current research on primary health care and national health insurance are reviewed together with unaddressed priorities that merit attention in the future. Factors that have facilitated or impeded progress with research utilization are reviewed and implications for health systems strengthening in Ghana and elsewhere in Africa and globally are discussed.
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Medical Assistance , Universal Health Insurance , Ghana , Government Programs , Health Policy , Humans , United StatesABSTRACT
Introduction: In sub-Saharan Africa, extensive migratory activities and interactions exist especially amongst unmanned cross-border communities between countries sharing common borders which complicate emergency public health interventions. Understanding the nature of these activities and interactions will help strengthen public health interventions and control of pandemics such as the Ebola outbreak and COVID-19. Objective: The study aimed to understand the nature of contiguous border communities' interactions and to seek community solutions for building efficient and resilient health systems to combat a possible Ebola outbreak in Ghana and Burkina Faso and the control of future pandemics. Methods: A qualitative cross sectional study design using focused group discussions and key informant interviews involving six focused groups and forty-six key informants were conducted amongst six Kasem-speaking contiguous border communities, three-each in Ghana and Burkina Faso. Findings: Findings of interactions consisted of social interactions such as marriage ceremonies; traditional and religious practices; informal trade; and health seeking behavior in the study communities. Collaborative disease surveillance systems; constructive dialogue involving community traditional leaders; incorporation of health education into social, traditional and religious activities; retraining of health personnel; effective communication including networking; and inter-governmental collaborations were identified as solutions to the effective control of the Ebola outbreak and for future public health interventions in general. Conclusion: Understanding community interactions and seeking community solutions were identified to be crucial in building efficient health systems that are resilient and responsive to the Ebola outbreak and for future pandemics in contiguous border communities in sub-Saharan Africa.
Subject(s)
Disease Outbreaks , Hemorrhagic Fever, Ebola , Pandemics , Africa, Western/epidemiology , Burkina Faso/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Ghana/epidemiology , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Humans , Pandemics/prevention & control , Qualitative ResearchABSTRACT
INTRODUCTION: In Northern Ghana, a combination of torrential rains coupled with the spilling of the Bagre dam in neighboring Burkina Faso in the past few years has resulted in perennial flooding of communities. This has often led to the National Disaster Management Organization (NADMAO) the main disaster responder agency in Ghana, being called upon to act. However affected communities have never had the opportunity to evaluate the activities of the agency. The aim of this study is therefore to assess the performance of the main responder agency by affected community members to improve on future disaster management. METHODS: A mixed qualitative design employing a modified form of the community score card methodology and focus group discussions was conducted in the 4 most affected communities during the last floods of 2012 in the Kasena-Nankana West district of the Upper East Region of Northern Ghana. Community members comprising of chiefs, elders, assembly members, women groups, physically challenged persons, farmers, traders and youth groups formed a group in each of the four communities. Generation and scoring of evaluative indicators was subsequently performed by each group through the facilitation of trained research assistants. Four Focus group discussions (FGDs) were also conducted with the group members in each community to get an in-depth understanding of how the responder agency performed in handling disasters. RESULTS: A total of four community score cards and four focus group discussions were conducted involving 48 community representatives. All four communities identified NADMO as the main responder agency during the last disaster. Indicators such as education/awareness, selection process of beneficiaries, networking/collaboration, timing, quantity of relief items, appropriateness, mode of distribution of relief items, investigation and overall performance of NADMO were generated and scored. The timing of response, quantity and appropriateness of relief items were evaluated as being poor whereas the overall performance of the responder agency was above average. CONCLUSION: NADMO was identified as the main responder agency during the last disasters with community members identifying education/awareness, selection process of beneficiaries, networking/collaboration, timing of response, quantity of relief items, appropriateness of relief items, mode of distribution of relief items, investigation and overall performance as the main evaluative indicators. The overall performance of NADMO was rated to be satisfactory. KEY WORDS: Kasena-Nankana West district, NADMO, community score card, Rural Northern Ghana.
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BACKGROUND: This study was conducted at the Kintampo Municipal Hospital in Ghana to determine whether there was any benefit (or otherwise) in basing the management of cases of suspected malaria solely on laboratory confirmation (microscopy or by RDT) as compared with presumptive diagnosis. METHOD: Children under five years who reported at the Out-Patient Department of the Hospital with axillary temperature ≥37.5°C or with a 48 hr history of fever were enrolled and had malaria microscopy and RDT performed. The attending clinician was blinded from laboratory results unless a request for these tests had been made earlier. Diagnosis of malaria was based on three main methods: presumptive or microscopy and/or RDT. Cost implication for adopting laboratory diagnosis or not was determined to inform malaria control programmes. RESULTS: In total, 936 children were enrolled in the study. Proportions of malaria diagnosed presumptively, by RDT and microscopy were 73.6% (689/936), 66.0% (618/936) and 43.2% (404/936) respectively. Over 50% (170/318) of the children who were RDT negative and 60% (321/532) who were microscopy negative were treated for malaria when presumptive diagnoses were used. Comparing the methods of diagnoses, the cost of malaria treatment could have been reduced by 24% and 46% in the RDT and microscopy groups respectively; the reduction was greater in the dry season (43% vs. 50%) compared with the wet season (20% vs. 45%) for the RDT and microscopy confirmed cases respectively. DISCUSSION/CONCLUSION: Over-diagnosis of malaria was prevalent in Kintampo during the period of the study. Though the use of RDT for diagnosis of malaria might have improved the quality of care for children, it appeared not to have a cost saving effect on the management of children with suspected malaria. Further research may be needed to confirm this.
Subject(s)
Malaria/diagnosis , Malaria/drug therapy , Adolescent , Adult , Antimalarials/economics , Antimalarials/therapeutic use , Child , Child, Preschool , Clinical Laboratory Techniques/economics , Clinical Laboratory Techniques/methods , Cross-Sectional Studies , Female , Ghana , Health Care Costs , Hospitals, District , Humans , Infant , Infant, Newborn , Malaria/economics , Male , Middle Aged , Sensitivity and Specificity , Young AdultABSTRACT
BACKGROUND: Venomous snakebites contribute to morbidity and mortality throughout the world, most commonly in resource-poor areas, with about 2.5 million humans sustaining snakebites annually. Coagulopathy is a significant cause of both morbidity and mortality in these patients. In the absence of more sophisticated hematological studies or obvious physical findings, many clinicians must rely on whole-blood clotting times to assess whether their patients are coagulopathic. Alternative (bedside) methods to assess clotting times are often officially recommended and used, but have not been validated. OBJECTIVE: We assessed two bedside methods for measuring whole-blood clotting time after snakebites for their congruence with results from a hospital laboratory. METHODS: Over a 5-month period, 46 sequential patients presenting with a possible snakebite had blood drawn for bedside (using syringe and ceftriaxone bottle as containers) and laboratory whole-blood clotting tests. All three tests used â¼5 mL whole blood and looked for any clot formation within 20 min. RESULTS: Compared to the laboratory, the syringe method correctly classified the patients 84.7% of the time (sensitivity 88.9%; specificity 82.4%). The bottle method correctly classified the patients 86.8% of the time (sensitivity 83.3%; specificity 90.0%). Comparing the area under the Receiver Operator Characteristics curves shows that both the syringe and bottle methods do not differ in their discrimination for identifying clotting. CONCLUSIONS: Both the syringe and ceftriaxone bottle bedside clotting test methods appear to be accurate enough to help guide therapy after potential snake envenomations when formal laboratory testing is unavailable.
Subject(s)
Snake Bites/blood , Area Under Curve , Humans , Point-of-Care Systems , Sensitivity and Specificity , Whole Blood Coagulation TimeABSTRACT
Acute spontaneous intra-abdominal hemorrhage can be life-threatening and is particularly challenging in resource-poor settings. A 35-year-old woman presented in acutely hypotensive with a distended, rigid abdomen. A paracentesis produced >10 mL of non-clotting blood and she was taken to the operating room where significant bleeding from a liver cancer nodule was identified. With no other option, the generalists doing the surgery used a novel technique - the omental patch - to stem the hemorrhage. The patient recovered from the surgery. The urgency of performing surgery for spontaneous intraperitoneal hemorrhage increases with the scarcity of transfusable blood and general medical officers' lack surgical experience. In this case, they rapidly improvised, innovatively adapting the omental patch procedure, normally used to close duodenal ulcers, to save a life. They had neither performed nor seen this procedure previously. An omental patch to stop massive localized intra-abdominal hemorrhage may be an important tool for all surgeons.
Subject(s)
Abdominal Cavity/physiopathology , Exsanguination/surgery , Liver Neoplasms/complications , Omentum/surgery , Adult , Exsanguination/etiology , Female , Humans , Liver Neoplasms/pathology , Paracentesis/methods , Treatment OutcomeABSTRACT
BACKGROUND: Subsidized antiretroviral therapy programs obviously lowers the cost of antiretroviral drugs but other major costs are still incurred, which makes the overall cost of accessing and consuming antiretroviral treatment very high and sometimes catastrophic. The objective of this study was to estimate the total cost to rural ambulating HIV/AIDS patients on highly active antiretroviral therapy in a rural area of the middle belt of Ghana. METHODS: This was a convenient cross-sectional study of people diagnosed with HIV/AIDS receiving outpatient care and carried out from September to October 2009 involving 80 HIV/AIDS patients on HAART. Data was derived from patients' medical records on health care utilization and a completed pre tested questionnaire used to obtain the cost of transportation and estimates of individual earned income from which the labor productivity loses (opportunity cost) for days not worked as a result of attending the antiretroviral clinic were derived. RESULTS: The median total, indirect and direct annual costs to rural ambulating HIV/AIDS patients on HAART were estimated to be $US71.18 (115.16 Ghana cedis), $US2.740 (3.92 Ghana cedis) and $US53.04 (75.00 Ghana cedis) respectively. CONCLUSION: Although the cost of antiretroviral drugs has been subsidized by government from $360 to $41.38 per annum, HIV/AIDS patients on HAART spend double of this subsidized amount out of their pocket seeking health care. We recommend that agencies associated with HIV/AIDS activities, supplements government's effort by helping to get antiretroviral closer to the door step of patients so as to reduce this huge financial burden which constitutes more than 100% of their median annual earned income.
Subject(s)
Ambulatory Care/economics , Antiretroviral Therapy, Highly Active/economics , HIV Infections/drug therapy , HIV Infections/economics , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/economics , Costs and Cost Analysis , Cross-Sectional Studies , Ghana , Humans , Pilot Projects , Retrospective Studies , Rural HealthABSTRACT
While umbilical hernias frequently occur during pregnancy, the few reported cases of uterine or fibroid incarceration in ventral hernias during pregnancy all involved incisional abdominal wall defects from prior laparotomies and Cesarean sections; none involved umbilical hernias. We discuss the case of a 42-year-old well-developed, well-nourished grand multiparous woman (G8P7) with a huge umbilical hernia containing a 38-week gravid uterus, as well as her management and the avoidance of known complications that have occurred in similar incisional hernia cases. Successful pregnancy outcomes can occur in cases of pregnancies in ventral hernias, even in resource-poor settings that have Cesarean section capabilities.
Subject(s)
Hernia, Umbilical/pathology , Pregnancy Complications/pathology , Uterus/pathology , Abdominal Wall/pathology , Adult , Cesarean Section/adverse effects , Female , Humans , Laparotomy/adverse effects , Pregnancy , Pregnancy OutcomeABSTRACT
BACKGROUND: The RTS,S/AS01(E) candidate malaria vaccine is being developed for immunisation of infants in Africa through the expanded programme on immunisation (EPI). 8 month follow-up data have been reported for safety and immunogenicity of RTS,S/AS01(E) when integrated into the EPI. We report extended follow-up to 19 months, including efficacy results. METHODS: We did a randomised, open-label, phase 2 trial of safety and efficacy of the RTS,S/AS01(E) candidate malaria vaccine given with EPI vaccines between April 30, 2007, and Oct 7, 2009, in Ghana, Tanzania, and Gabon. Eligible children were 6-10 weeks of age at first vaccination, without serious acute or chronic illness. All children received the EPI diphtheria, tetanus, pertussis (inactivated whole-cell), and hepatitis-B vaccines, Haemophilus influenzae type b vaccine, and oral polio vaccine at study months 0, 1, and 2, and measles vaccine and yellow fever vaccines at study month 7. Participants were randomly assigned (1:1:1) to receive three doses of RTS,S/AS01(E) at 6, 10, and 14 weeks (0, 1, 2 month schedule) or at 6 weeks, 10 weeks, and 9 months (0, 2, 7 month schedule) or placebo. Randomisation was according to a predefined block list with a computer-generated randomisation code. Detection of serious adverse events and malaria was by passive case detection. Antibodies against Plasmodium falciparum circumsporozoite protein and HBsAg were monitored for 19 months. This study is registered with ClinicalTrials.gov, number NCT00436007. FINDINGS: 511 children were enrolled. Serious adverse events occurred in 57 participants in the RTS,S/AS01(E) 0, 1, 2 month group (34%, 95% CI 27-41), 47 in the 0, 1, 7 month group (28%, 21-35), and 49 (29%, 22-36) in the control group; none were judged to be related to study vaccination. At month 19, anticircumsporozoite immune responses were significantly higher in the RTS,S/AS01(E) groups than in the control group. Vaccine efficacy for the 0, 1, 2 month schedule (2 weeks after dose three to month 19, site-adjusted according-to-protocol analysis) was 53% (95% CI 26-70; p=0·0012) against first malaria episodes and 59% (36-74; p=0·0001) against all malaria episodes. For the entire study period, (total vaccinated cohort) vaccine efficacy against all malaria episodes was higher with the 0, 1, 2 month schedule (57%, 95% CI 33-73; p=0·0002) than with the 0, 1, 7 month schedule (32% CI 16-45; p=0·0003). 1 year after dose three, vaccine efficacy against first malaria episodes was similar for both schedules (0, 1, 2 month group, 61·6% [95% CI 35·6-77·1], p<0·001; 0, 1, 7 month group, 63·8% [40·4-78·0], p<0·001, according-to-protocol cohort). INTERPRETATION: Vaccine efficacy was consistent with the target put forward by the WHO-sponsored malaria vaccine technology roadmap for a first-generation malaria vaccine. The 0, 1, 2 month vaccine schedule has been selected for phase 3 candidate vaccine assessment. FUNDING: Program for Appropriate Technology in Health Malaria Vaccine Initiative; GlaxoSmithKline Biologicals.
Subject(s)
Antibodies, Protozoan/blood , Malaria Vaccines/adverse effects , Malaria Vaccines/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/prevention & control , Protozoan Proteins/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Female , Follow-Up Studies , Gabon/epidemiology , Ghana/epidemiology , Haemophilus Vaccines/administration & dosage , Hepatitis B Vaccines/administration & dosage , Humans , Immunization Programs , Immunization Schedule , Infant , Malaria Vaccines/administration & dosage , Malaria, Falciparum/diagnosis , Malaria, Falciparum/epidemiology , Male , Poliovirus Vaccine, Oral/administration & dosage , Program Evaluation , Severity of Illness Index , Tanzania/epidemiology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01(E) or the oil-in-water based adjuvant AS02(D) induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults. METHODS: This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01(E) and RTS,S/AS02(D) in children aged 5-17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites. RESULTS: Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01(E) induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01(E) induced higher CD4 T cell responses as compared to RTS,S/AS02(D) when given on a 0,1,7-month schedule. CONCLUSIONS: These findings support further Phase III evaluation of RTS,S/AS01(E). The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230.
Subject(s)
Malaria Vaccines/immunology , T-Lymphocytes/immunology , Antibodies, Protozoan/biosynthesis , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Child , Child, Preschool , Cytokines/metabolism , Flow Cytometry , Ghana , Humans , Infant , Malaria Vaccines/administration & dosageABSTRACT
BACKGROUND: The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). METHODS: This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. RESULTS: The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. CONCLUSION: RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).
Subject(s)
Immunization/methods , Malaria Vaccines/adverse effects , Malaria Vaccines/immunology , Bacterial Capsules/administration & dosage , Bacterial Capsules/adverse effects , Bacterial Capsules/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/adverse effects , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Female , Gabon , Ghana , Haemophilus Vaccines/administration & dosage , Haemophilus Vaccines/adverse effects , Haemophilus Vaccines/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/adverse effects , Hepatitis B Vaccines/immunology , Humans , Immunization, Secondary/methods , Infant , Malaria Vaccines/administration & dosage , Male , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/adverse effects , Poliovirus Vaccine, Oral/immunology , TanzaniaABSTRACT
BACKGROUND: The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01(E) and RTS,S/AS02(D) in infants and young children 5-17 months of age in Ghana. METHODOLOGY: A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01(E) or rabies vaccine at one center and RTS,S/AS01(E) or RTS,S/AS02(D) at the other. For the other schedules at both study sites, they received RTS,S/AS01(E) or RTS,S/AS02(D). The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1. RESULTS: The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS,S/AS01(E) vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01(E) than RTS,S/AS02(D). Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01(E) compared to RTS,S/AS02(D) had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01(E) schedules. CONCLUSIONS: Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01(E) than RTS,S/AS02(D) and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01(E) and a 3 dose schedule for further development in children and infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360230.