An impact assessment of the use of aerial logistics to improve access to vaccines in the Western-North Region of Ghana.

BACKGROUND: Prevention of infectious diseases among children is crucial to improve child health and survival. However, many countries in Sub-Saharan Africa struggle to achieve vaccination targets due to supply chain challenges, which lead to vaccine shortages, stockouts, and increased costs. We evaluated the effects of aerial logistics (centralized storage and delivery by drones) on vaccine stock, stockouts, vaccination coverage and vaccine preventable outcomes in the Western North Region of Ghana. METHODS: The study combined retrospective quasi-experimental and cross-sectional designs to evaluate supply chain, programmatic, and clinical outcomes. Surveys to health providers were used to collect information from a random sample of 156 facilities, and secondary data on vaccination coverage and clinical outcomes was analyzed at the district level for the years 2017-2021. RESULTS: Facilities served by aerial logistics reported significant reductions in the duration of vaccine stockouts (30 %, p-value < 0.05), as well as in the frequency of missed opportunities for vaccination (44 %, p-value < 0.05). Being served by aerial logistics was associated with increased satisfaction with access to vaccines. Significant differences in vaccination coverage were found for most vaccines, in a range between 13.1 and 37.5 percentage points in vaccination coverage for served districts. Infectious diarrhea cases in children between 5 and 9 years old were reduced by 41.6 % (p-value < 0.05). CONCLUSION: End-to-end aerial logistics appears as an effective tool to improve the performance of the supply chain for vaccines. The strategy potentially increases the resilience of the health system and contributes to increased vaccination coverage and higher levels of satisfaction among providers in the Western North Region of Ghana.

Quality of Care: A Review of Maternal Deaths in a Regional Hospital in Ghana.

The government of Ghana and key stakeholders have put into place several interventions aimed at reducing maternal deaths. At the institutional level, the conduct of maternal deaths audit has been instituted. This also contributes to reducing maternal deaths as shortcomings that may have contributed to such deaths could be identified to inform best practice and forestall such occurrences in the future. The objective of this study was to review the quality of maternal care in a regional hospital. A review of maternal deaths using Quality of Care Evaluation Form adapted from the Komfo Anokye Teaching Hospital (KATH) Maternal Death Audit Evaluation Committee was used. About fifty-five percent, 18 (55%) of cases were deemed to have received adequate documentation, senior clinicians were involved in 26(85%) of cases. Poor documentation, non-involvement of senior clinicians in the management of cases, laboratory related issues particularly in relation to blood and blood products as well as promptness of care and adequacy of intensive care facilities and specialists in the hospital were contributory factors to maternal deaths . These are common themes contributing to maternal deaths in developing countries which need to be urgently tackled. Maternal death review with emphasis on quality of care, coupled with facility gap assessment, is a useful tool to address the adequacy of emergency obstetric care services to prevent further maternal deaths.

Biochemical and hematologic parameters for children in the middle belt of Ghana.

Reference values derived from developed countries are used in many countries in Africa for interpretation of laboratory results obtained during routine healthcare and clinical trials. Use of locally derived reference values has been recommended. The purpose of the study was to establish age- and sex-specific reference values for children in the middle belt of Ghana. Reference values were determined for 21 biochemical and 18 hematologic parameters by using Clinical and Laboratory Standards Institute C28-A3 guidelines in a sample of 1,442 healthy children. Hemoglobin, hematocrit, mean cell volume, erythrocytes, urea, and creatinine were lower when compared with values from northern countries but alanine aminotransferase, aspartate aminotransferase, and total bilirubin were higher. A panel of locally relevant age- and sex-specific reference values was established for commonly used biochemical and hematologic tests in children in the middle part of Ghana. This will help in interpretation of laboratory results for clinical management of patients, screening, and safety monitoring during clinical trials.

The benefits or otherwise of managing malaria cases with or without laboratory diagnosis: the experience in a district hospital in Ghana.

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.

Duodenal perforation in a 12-month old child with severe malaria.

Peptic ulcer disease (PUD) in children remains rare and difficult to diagnose before the onset of complications. We report on a case of a 12-month child with perforated duodenal ulcer, association with malaria. The severity of the febrile presentation and the positive laboratory confirmation of malaria delayed the diagnosis of PUD. Surgical intervention was successful and without significant sequelae. An awareness of the possibility, and a lower threshold for considering PUD in children may help prevent complications.

Haematological and biochemical reference values for healthy adults in the middle belt of Ghana.

BACKGROUND: Reference values are very important in clinical management of patients, screening participants for enrollment into clinical trials and for monitoring the onset of adverse events during these trials. The aim of this was to establish gender-specific haematological and biochemical reference values for healthy adults in the central part of Ghana. METHODS: A total of 691 adults between 18 and 59 years resident in the Kintampo North Municipality and South District in the central part of Ghana were randomly selected using the Kintampo Health and Demographic Surveillance System and enrolled in this cross-sectional survey. Out of these, 625 adults made up of 316 males and 309 females were assessed by a clinician to be healthy. Median values and nonparametric 95% reference values for 16 haematology and 22 biochemistry parameters were determined for this population based on the Clinical Laboratory and Standards Institute guidelines. Values established in this study were compared with the Caucasian values being used currently by our laboratory as reference values and also with data from other African and western countries. RESULTS: REFERENCE VALUES ESTABLISHED INCLUDE: haemoglobin 113-164 g/L for males and 88-144 g/L for females; total white blood cell count 3.4-9.2 × 10(9)/L; platelet count 88-352 × 10(9)/L for males and 89-403 × 10(9)/L for females; alanine aminotransferase 8-54 U/L for males and 6-51 U/L for females; creatinine 56-119 µmol/L for males and 53-106 µmol/L for females. Using the haematological reference values based on the package inserts would have screened out up to 53% of potential trial participants and up to 25% of the population using the biochemical parameters. CONCLUSION: We have established a panel of locally relevant reference parameters for commonly used haematological and biochemical tests. This is important as it will help in the interpretation of laboratory results both for clinical management of patients and safety monitoring during a trial.

Safety and efficacy of the RTS,S/AS01E candidate malaria vaccine given with expanded-programme-on-immunisation vaccines: 19 month follow-up of a randomised, open-label, phase 2 trial.

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.

T cell responses to the RTS,S/AS01(E) and RTS,S/AS02(D) malaria candidate vaccines administered according to different schedules to Ghanaian children.

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.

Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization.

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).

Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children.

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.

Capillary refill time as an independent prognostic indicator in severe and complicated malaria.

OBJECTIVES: To improve algorithms for the identification of children at risk of dying of malaria in endemic areas. STUDY DESIGN: In a prospective study of 2446 children with severe and complicated malaria admitted to a tertiary referral center in Ghana, West Africa, 12 clinical and laboratory signs were evaluated as indicators of death. RESULTS: A prolonged (> 2 seconds) capillary refill time (pCRT) was identified as an independent prognostic indicator of death along with acidosis, coma, and respiratory distress. Among the clinical signs, pCRT increased the risk of dying from 4-fold to 11-fold when present in addition to coma and respiratory distress. CONCLUSIONS: The recognition of pCRT as an independent indicator of death justifies its inclusion as a defining criterion of severe and complicated malaria and improves the use of clinical examinations in the triage of patients with malaria. As pCRT has been shown to reflect circulatory disturbances in children, it should be included in upcoming studies as a possible sign to indicate the need for intravenous fluid administration.