Surveillance and laboratory collaboration in response to an outbreak of Vibrio parahaemolyticus, Plesiomonas shigelloides, and Aeromonas hydrophila in Sekondi-Takoradi, Ghana: a case series.

BACKGROUND: The detection of epidemic-prone pathogens is important in strengthening global health security. Effective public health laboratories are critical for reliable, accurate, and timely testing results in outbreak situations. Ghana received funding as one of the high-risk non-Ebola affected countries to build and strengthen public health infrastructure to meet International Health Regulation core capacities. A key objective was to build laboratory capacities to detect epidemic-prone diseases. CASE PRESENTATION: In June 2018, a local hospital received eight patients who presented with acute diarrhea. A sample referral system for Ghana has not been established, but the Sekondi Zonal Public Health Laboratory staff and mentors collaborated with Disease Surveillance Officers (DSOs) to collect, package, and transport stool specimens from the outbreak hospital to the Public Health Laboratory for laboratory testing. The patients included seven females and one male, of Fante ethnicity from the Fijai township of Sekondi-Takoradi Municipality. The median age of the patients was 20 years (interquartile range: 20-29 years). Vibrio parahaemolyticus was identified within 48 hours from four patients, Plesiomonas shigelloides from one patient, and Aeromonas hydrophila from another patient. There was no bacteria growth from the samples from the two other patients. All patients were successfully treated and discharged. CONCLUSION: This is the first time these isolates have been identified at the Sekondi Zonal Public Health Laboratory, demonstrating how rapid response, specimen transportation, laboratory resourcing, and public health coordination are important in building capacity towards achieving health security. This capacity building was part of the United States Centers for Disease Control and Prevention engagement of international and local partners to support public health laboratories with supplies, diagnostic equipment, reagents, and logistics.

Common bacteria in sputum or gastric lavage of patients presenting with signs and symptoms of lower respiratory tract infections.

INTRODUCTION: lower respiratory tract infections (LRTIs) are infections involving the trachea, primary bronchi and lungs. People with LRTIs typically experience coughs as the primary symptoms; however, shortness of breath, weakness, fever and fatigue may be coupled with the cough. It is common among the aged, children under five and the immune-suppressed. Persons with symptoms suggestive of pulmonary tuberculosis (TB) may have tuberculosis, other respiratory tract infection or co-infection of tuberculosis and other respiratory pathogens. This study aimed to identify the presence of pathogens in sputum of suspected tuberculosis cases and their antimicrobial resistance patterns. METHODS: this was a retrospective study conducted from September 2018 to November 2019 at Tamale Public Health Laboratory. Sputum or gastric lavage samples were collected from persons with suspected clinical presentations of TB and/or LRTI. These samples were cultured using standard microbiological protocols and antimicrobial susceptibility test performed on the positive cultures by Kirby-Bauer disc diffusion method. Molecular identification of M. tuberculosis was performed on all the suspected TB cases using GeneXpert mycobacterium tuberculosis/rifampin (MTB/RIF) assay. RESULTS: during the study period, there were 264 cases of which 49.2% were males and 50.8% were females. Positive cases for culture were 47.3%. Out of the 264 cases, 186 (70.5%) were suspected TB with 51.6% being positive for culture, 6.5% positive for M. tuberculosis (GeneXpert confirmed) and 3.8% co-infection of TB with other bacteria pathogens. Klebsiella spp. (35/125; 28%) and Pseudomonas spp. (19/125; 15.2%) were the most predominant pathogens isolated. There was no significant difference in detection of bacteria in males and females (p=0.89), however individuals with suspected TB were significantly infected with other bacterial species than the unsuspected individuals (p=0.03). Almost all the isolates showed high susceptibility towards carbapenem (meropenem) and high resistance towards the third generation cephalosporins (cefotaxime and ceftriaxone). CONCLUSION: this study highlights the need to test individuals with classical symptoms of LRTIs for other bacterial infections other than TB only. Sputum culture is recommended for all suspected tuberculosis cases to provide accurate laboratory diagnosis to LRTIs and mitigate unnecessary use of antimicrobials.

Immunogenicity and safety of the RTS,S/AS01 malaria vaccine co-administered with measles, rubella and yellow fever vaccines in Ghanaian children: A phase IIIb, multi-center, non-inferiority, randomized, open, controlled trial.

BACKGROUND: To optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines. METHODS: In this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5. RESULTS: Non-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups. CONCLUSIONS: RTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.

Long-term immunogenicity and immune memory response to the hepatitis B antigen in the RTS,S/AS01E malaria vaccine in African children: a randomized trial.

RTS,S/AS01E malaria vaccine contains the hepatitis B virus surface antigen and may thus serve as a potential hepatitis B vaccine. To evaluate the impact of RTS,S/AS01E when implemented in the Expanded Program of Immunization, infants 8-12 weeks old were randomized to receive either RTS,S/AS01E or a licensed hepatitis B control vaccine (HepB), both co-administered with various combinations of the following childhood vaccines: diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type b, trivalent oral poliovirus, pneumococcal non-typeable Haemophilus influenzae protein D conjugate and human rotavirus vaccine. Long-term persistence of antibodies against the circumsporozoite (CS) protein and hepatitis B surface antigen (HBsAg) were assessed, together with the immune memory response to the HB antigen following a booster dose of HepB vaccine. Subgroups receiving RTS,S or the HepB control vaccine were pooled into RTS,S groups and HepB groups, respectively. One month post-HepB booster vaccination, 100% of participants in the RTS,S groups and 98.3% in the control groups had anti-HBs antibody concentrations ≥10 mIU/mL with the geometric mean concentrations (GMCs) at 46634.7 mIU/mL (95% CI: 40561.3; 53617.6) and 9258.2 mIU/mL (95% CI: 6925.3; 12377.0), respectively. Forty-eight months post-primary vaccination anti-CS antibody GMCs ranged from 2.3 EU/mL to 2.7 EU/mL in the RTS,S groups compared to 1.1 EU/mL in the control groups. Hepatitis B priming with the RTS,S/AS01E vaccine was effective and resulted in a memory response to HBsAg as shown by the robust booster response following an additional dose of HepB vaccine. RTS,S/AS01E when co-administered with PHiD-CV, HRV and other childhood vaccines, had an acceptable safety profile.

Immune response to the hepatitis B antigen in the RTS,S/AS01 malaria vaccine, and co-administration with pneumococcal conjugate and rotavirus vaccines in African children: A randomized controlled trial.

The RTS,S/AS01 malaria vaccine (Mosquirix) reduces the incidence of Plasmodium falciparum malaria and is intended for routine administration to infants in Sub-Saharan Africa. We evaluated the immunogenicity and safety of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix) and human rotavirus vaccine (HRV; Rotarix) when co-administered with RTS,S/AS01 ( www.clinicaltrials.gov NCT01345240) in African infants. 705 healthy infants aged 8-12 weeks were randomized to receive three doses of either RTS,S/AS01 or licensed hepatitis B (HBV; Engerix B) vaccine (control) co-administered with diphtheria-tetanus-acellular pertussis-Haemophilus influenzae type-b-conjugate vaccine (DTaP/Hib) and trivalent oral poliovirus vaccine at 8-12-16 weeks of age, because DTaP/Hib was not indicated before 8 weeks of age. The vaccination schedule can still be considered broadly applicable because it was within the age range recommended for EPI vaccination. PHiD-CV or HRV were either administered together with the study vaccines, or after a 2-week interval. Booster doses of PHiD-CV and DTaP/Hib were administered at age 18 months. Non-inferiority of anti-HBV surface antigen antibody seroprotection rates following co-administration with RTS,S/AS01 was demonstrated compared to the control group (primary objective). Pre-specified non-inferiority criteria were reached for PHiD-CV (for 9/10 vaccine serotypes), HRV, and aP antigens co-administered with RTS,S/AS01 as compared to HBV co-administration (secondary objectives). RTS,S/AS01 induced a response to circumsporozoite protein in all groups. Pain and low grade fever were reported more frequently in the PHiD-CV group co-administered with RTS,S/AS01 than PHiD-CV co-administered with HBV. No serious adverse events were considered to be vaccine-related. RTS,S/AS01 co-administered with pediatric vaccines had an acceptable safety profile. Immune responses to RTS,S/AS01 and to co-administered PHiD-CV, pertussis antigens and HRV were satisfactory.

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.

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.