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2. Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites
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Agnandji, ST, Lell, B, Fernandes, JF, Abossolo, BP, Kabwende, AL, Adegnika, AA, Mordmueller, B, Issifou, S, Kremsner, PG, Loembe, MM, Sacarlal, J, Aide, P, Madrid, L, Lanaspa, M, Mandjate, S, Aponte, JJ, Bulo, H, Nhama, A, Macete, E, Alonso, P, Abdulla, S, Salim, N, Mtoro, AT, Mutani, P, Tanner, M, Mavere, C, Mwangoka, G, Lweno, O, Juma, OA, Shekalaghe, S, Tinto, H, D'Alessandro, U, Sorgho, H, Valea, I, Ouedraogo, JB, Lompo, P, Diallo, S, Traore, O, Bassole, A, Dao, E, Hamel, MJ, Kariuki, S, Oneko, M, Odero, C, Otieno, K, Awino, N, Muturi-Kioi, V, Omoto, J, Laserson, KF, Slutsker, L, Otieno, W, Otieno, L, Otsyula, N, Gondi, S, Otieno, A, Ogutu, B, Ochola, J, Onyango, I, Oyieko, J, Njuguna, P, Chilengi, R, Akoo, P, Kerubo, C, Maingi, C, Olotu, A, Bejon, P, Marsh, K, Mwabingu, G, Gitaka, J, Owusu-Agyei, S, Asante, KP, Boahen, O, Dosoo, D, Adjei, G, Adeniji, E, Yawson, AK, Kayan, K, Chandramohan, D, Greenwood, B, Lusingu, J, Gesase, S, Malabeja, A, Abdul, O, Mahende, C, Liheluka, E, Lemnge, M, Theander, TG, Drakeley, C, Mbwana, J, Ansong, D, Agbenyega, T, Adjei, S, Boateng, HO, Rettig, T, Bawa, J, Sylverken, J, Sambian, D, Sarfo, A, Agyekum, A, Martinson, F, Hoffman, I, Mvalo, T, Kamthunzi, P, Nkomo, R, Tembo, T, Tsidya, GTM, Kilembe, J, Chawinga, C, Ballou, WR, Cohen, J, Guerra, Y, Jongert, E, Lapierre, D, Leach, A, Lievens, M, Ofori-Anyinam, O, Olivier, A, Vekemans, J, Kaslow, D, Leboulleux, D, Savarese, B, Schellenberg, D, and Partnership, RTSSCT
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Pediatrics ,medicine.medical_specialty ,030231 tropical medicine ,Plasmodium falciparum ,Immunology ,03 medical and health sciences ,0302 clinical medicine ,parasitic diseases ,Vaccine Development ,Malaria Vaccines ,medicine ,Prevalence ,Medicine and Health Sciences ,Parasitic Diseases ,Humans ,Malaria, Falciparum ,Adverse effect ,Africa South of the Sahara ,030304 developmental biology ,0303 health sciences ,Vaccines ,Intention-to-treat analysis ,Malaria vaccine ,business.industry ,Incidence ,Vaccination ,1. No poverty ,RTS,S ,Immunity ,Infant ,Biology and Life Sciences ,General Medicine ,medicine.disease ,Vaccine efficacy ,Tropical Diseases ,Vaccination and Immunization ,3. Good health ,Malaria ,Infectious Diseases ,Medicine ,Clinical Immunology ,business ,Meningitis ,Research Article - Abstract
Mary Hamel and colleagues in the RTS,S Clinical Trials Partnership report updated safety and efficacy results from an ongoing Phase 3 trial, including calculations of vaccine impact (malaria cases prevented). Please see later in the article for the Editors' Summary, Background A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission. Methods and Findings 6,537 infants aged 6–12 wk and 8,923 children aged 5–17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p, Editors' Summary Background Every year, more than 200 million cases of malaria occur worldwide, and more than 600,000 people, mainly children living in sub-Saharan Africa, die from this parasitic disease. Malaria parasites are transmitted to people through the bites of infected night-flying mosquitoes and cause fever that needs to be treated promptly with anti-malarial drugs to prevent anemia (a reduction in red blood cell numbers) and life-threatening organ damage. Malaria transmission can be prevented by using long-lasting insecticides sprayed on the indoor walls of homes to kill the mosquitoes that spread the malaria parasite or by sleeping under insecticide-treated nets to avoid mosquito bites and further reduce mosquito numbers. Widespread use of these preventative measures, together with the introduction of artemisinin combination therapy (an effective anti-malarial treatment), has reduced the global burden of malaria by 45% in all age groups, and by 51% among young children, since 2000. Why Was This Study Done? Unfortunately, the emergence of insecticide and drug resistance is threatening this advance in malaria control. Moreover, additional interventions—specifically, effective malaria vaccines—will be needed to eliminate malaria in the large areas of Africa where malaria transmission remains high. Currently, there is no licensed malaria vaccine, but RTS,S/AS01, the most advanced malaria vaccine candidate, is undergoing phase 3 clinical trials (the last stage of testing before licensing) in infants and children in seven African countries. The RTS,S Clinical Trials Partnership reported encouraging results on the efficacy and safety of RTS,S/AS01 during 12 months of follow-up in 2011 and 2012. Here, researchers report on the 18-month efficacy and safety of RTS,S/AS01. Vaccine efficacy (VE) is the reduction in the incidence of a disease (the number of new cases that occur in a population in a given period) among trial participants who receive the vaccine compared to the incidence among participants who do not receive the vaccine. What Did the Researchers Do and Find? The researchers randomly assigned 6,537 infants aged 6–12 weeks and 8,923 children aged 5–17 months to receive three doses of RTS,S/AS01 or a control vaccine. During 18 months of follow-up, there were 0.69 episodes of clinical malaria (a high temperature and parasites in the blood) per person-year among the children who received all the planned doses of RTS,S/AS01 (the “per protocol” population) and 1.17 episodes per person-year among the control children—a VE against clinical malaria in the per-protocol population of 46%. A similar VE was seen in an intention-to-treat analysis that included all the enrolled children, regardless of whether they received all of the planned vaccine doses; intention-to-treat analyses reflect the real-life situation—in which children sometimes miss vaccine doses—better than per-protocol analyses. In intention-to-treat analyses, the VE among children against severe malaria (fever, parasites in the blood, and symptoms such as anemia) and hospitalization for malaria was 34% and 41%, respectively. Among infants, the VE against clinical malaria was 27% in both per-protocol and intention-to-treat analyses; the vaccine showed no protection against severe malaria or hospitalization. In both infants and children, VE waned with time since vaccination. Across all the study sites, RTS,S/AS01 averted an average of 829 and 449 cases of clinical malaria per 1,000 children and infants vaccinated, respectively. Finally, the serious adverse event meningitis (inflammation of the tissues lining the brain and spinal cord) occurred more frequently in trial participants given RTS,S/AS01 than in those given the control vaccine, but the incidence of other serious adverse events was similar in both groups of participants. What Do These Findings Mean? These and other findings show that, during 18 months of follow-up, vaccination of children and young infants with RTS,S/AS01 prevented many cases of clinical and severe malaria and that the impact of vaccination was highest in regions with the highest incidence of malaria. They indicate, as in the earlier analysis, that the VE against clinical and severe malaria is higher in children than in young infants and suggest that protection wanes over time. Whether or not the vaccine played a causal role in the observed cases of meningitis cannot be determined from these results, and the occurrence of meningitis will be followed closely during the remainder of the trial. Other study limitations (for example, variations in the clinical characteristics of participants from one center to another) may also affect the accuracy of these findings and their interpretation. However, by showing that even a modest VE can avert a substantial number of malaria cases, these findings suggest that vaccination with RTS,S/AS01 could have a major public health impact in sub-Saharan Africa. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001685. Information is available from the World Health Organization on all aspects of malaria (in several languages), including malaria immunization; the World Malaria Report 2013 provides details of the current global malaria situation; the World Health Organization also provides information on its Global Immunization Vision and Strategy (in English and French) The US Centers for Disease Control and Prevention provides information on malaria, including a selection of personal stories about malaria Information is available from the Roll Back Malaria Partnership on the global control of malaria and on the Global Malaria Action Plan (in English and French); its website includes a fact sheet about malaria in Africa The latest results from the phase 3 trial of RTS,S are available on the website of the PATH Malaria Vaccine Initiative, a global program of the international nonprofit organization PATH that aims to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world MedlinePlus provides links to additional information on malaria and on immunization (in English and Spanish)
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- 2014
3. Approaching the community about screening children for a multicentre malaria vaccine trial
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Lang, Trudie, Gould, Jayne, von Seidlein, Lorenz, Lusingu, John, Mshamu, S., Ismael, Sadiki, Liheluka, E., Kamuya, D., Mwachiro, D., Olotu, Ally, Njuguna, Patricia, Bejon, Phillip, Marsh, Kevin, Marsh, V, Molyneux, C., Lang, Trudie, Gould, Jayne, von Seidlein, Lorenz, Lusingu, John, Mshamu, S., Ismael, Sadiki, Liheluka, E., Kamuya, D., Mwachiro, D., Olotu, Ally, Njuguna, Patricia, Bejon, Phillip, Marsh, Kevin, Marsh, V, and Molyneux, C.
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- 2012
4. Understanding pre-hospital disease management of fever and diarrhoea in children-Care pathways in rural Tanzania.
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Lamshöft MM, Liheluka E, Ginski G, Lusingu JPA, Minja D, Gesase S, Mbwana J, Gesase G, Rautman L, Loag W, May J, Dekker D, and Krumkamp R
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- Humans, Tanzania epidemiology, Cross-Sectional Studies, Child, Preschool, Female, Male, Infant, Parents, Malaria drug therapy, Adult, Anti-Bacterial Agents therapeutic use, Fever drug therapy, Fever therapy, Diarrhea therapy, Diarrhea drug therapy, Rural Population
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Objective: Many children in sub-Saharan Africa die from infectious diseases like malaria, pneumonia, and diarrhoea that can be prevented by early diagnosis, effective and targeted treatment. This study aimed to gain insights into case management practices by parents before they present their children to hospital., Methods: We conducted a cross-sectional study among 332 parents attending a district hospital with their under-fives symptomatic with fever and/or diarrhoea between November 2019 and July 2020 in rural Tanzania. Timely and targeted treatment was defined as seeking health care within 24 h of fever onset, and continued fluid intake in case of diarrhoea., Results: The main admission diagnoses were acute respiratory infections (61.8%), malaria (25.3%), diarrhoea (18.4%) and suspected sepsis (8.1%). The majority of children (91%) received treatment prior to admission, mostly antipyretics (75.6%), local herbal medicines (26.8%), and antibiotics (17.8%)-half of them without prescription from a clinician. For diarrhoea, the use of oral rehydration solution was rare (9.0%), although perceived as easily accessible and affordable. 49.4% of the parents presented their children directly to the hospital, 23.2% went to a pharmacy/drug shop and 19.3% to a primary health facility first. Malaria symptoms began mostly 3 days before the hospital visit; only 25.4% of febrile children visited any health facility within 24 h of disease onset. Prior use of local herbal medicine (AOR = 3.2; 95% CI 1.4-7.3), visiting the pharmacy (adjusted Odds Ratio [AOR] = 3.1; 95% confidence interval [CI]: 1.0-9.8), the dispensary being the nearest health facility (AOR = 3.0; 95% CI: 1.5-6.2), and financial difficulties (AOR = 2.2; 95% CI 1.1-4.5) were associated with delayed treatment., Conclusion: This study suggests that antipyretics and antibiotics dispensed at pharmacies/drug shops, as well as use of local herbal medicines, delay early diagnosis and treatment, which can be life-threatening. Pharmacies/drug shops could be integrated as key focal points for sensitising community members on how to respond to paediatric illnesses and encourage the use of oral rehydration solutions., (© 2024 The Authors Tropical Medicine & International Health published by John Wiley & Sons Ltd.)
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- 2024
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5. Medicinal plants for treatment of diarrhoeal diseases among under-five children: experience from traditional healers in North-eastern Tanzania.
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Liheluka E, Gibore NS, Lusingu JPA, Gesase S, Minja DTR, Lamshöft M, Dekker D, and Bali T
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- Humans, Child, Phytotherapy, Traditional Medicine Practitioners, Tanzania, Medicine, African Traditional, Diarrhea drug therapy, Plants, Medicinal
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Background: Right through history, humans have relied heavily on plants for sustenance and the healing of different ailments. One of the long-standing traditions that communities have inherited from earlier generations is the use of herbal medicines for the treatment of paediatric ailments, including diarrhoea. This study showcased medicinal plants used by traditional healers for the treatment of diarrhoeal diseases among under-five children in North-eastern Tanzania., Methods and Design: A qualitative research approach and a narrative research design were employed. The research was carried out in the districts of Korogwe and Handeni in North-eastern Tanzania, with 52 in-depth interviews performed with participants (traditional healers). Purposive sampling method was used to select participants, and a thematic analysis framework was used to analyze the data., Results: Study results indicate that traditional healers had enormous insights and were well informed about medicinal plants that were perceived to be efficacious in treating diarrhoeal diseases among under-five children. A total of 54 medicinal plants were reported by the participants to be effective in healing diarrhoeal diseases among under-five children. However, out of 54 medicinal plants, 15 were predominantly disclosed by the majority of participants. Those medicinal plants include Psidium guajava, Rhus natalensis, Ozoroa insignis, Tamarindus indica, Ocimum suave, Combretum molle, Zanha africana, Solanum incanum, and Ximenia americana. Other medicinal plants mentioned by most participants include, Ochna holstii, Elaeodendron schlechterianum, Albizia anthelmintica, Commiphora pteleifolia, Salacia stuhlmanniana, and Zenkerella grotei., Conclusion: All traditional healers seemed to have a clear understanding regarding the medicinal plants that were used to treat diarrhoeal diseases among under-five children. The participants acknowledged to treating under-five children with diarrhoeal diseases using herbal medications on multiple occasions. The findings of this study should inspire more in-depth botanical research to determine whether the medicinal plants reported in this study have anti-diarrhoeal properties., (© 2023. BioMed Central Ltd., part of Springer Nature.)
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- 2023
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6. Community perceptions on the effectiveness of herbal medicines and factors associated with their use in managing diarrhoea among under-five children in North-eastern Tanzania.
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Liheluka E, Gibore NS, Lusingu JPA, Gesase S, Minja DTR, Lamshöft M, Dekker D, and Bali T
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Background: The demand for herbal medicines continues to increase globally. However, community perceptions on their effectiveness and factors influencing their use have not been extensively investigated, notably in the Tanga Region, North-eastern Tanzania, where their use in treating various diseases, including paediatric diarrhoea, has flourished. According to studies, Tanga Region has a high prevalence of diarrhoea among under-five children. This study explored community perceptions on the effectiveness of herbal medicines and factors associated with their use in managing diarrhoea among under-five children in North-eastern Tanzania., Methods: A qualitative approach and a narrative design were employed by the present study since they had the potential to reveal unrecognized or unreported research problems. Focus group discussions and in-depth interviews were used to facilitate data collection from June 2022 to February 2023. The methods were chosen since they are the most common sources of qualitative data in health research. Purposive sampling method was used to select 247 participants, which included 171 caretakers, 52 traditional healers, and 24 paediatric health workers. Interviews were conducted until the saturation point was reached. The purposive technique was considered since it was a method that enabled the researcher to select participants who were knowledgeable about the study topic. Data analysis was performed using thematic analysis., Results: Economic hardship, culture and heritage, superstitious beliefs, failure to recover after receiving hospital medication, easy accessibility of herbal medicines, and long distance to the health facility were the factors perceived to be potentially associated with persistent use of herbal medicines among caretakers. The majority of participants believed that herbal treatments were harmless and effective in treating diarrhoea., Conclusion: Superstitious beliefs, culture, and heritage were the primary justifications for using herbal medicines. It is vital for the relevant authority to educate the community on the risk of using unproven herbal medicines in order to diminish the effects that may arise from using uninvestigated herbs. As things stand, the use of herbal medications will continue owing to their relevance to the lives of people in the study setting., (© 2023. Japanese Society of Tropical Medicine.)
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- 2023
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7. Implementation research of a cluster randomized trial evaluating the implementation and effectiveness of intermittent preventive treatment for malaria using dihydroartemisinin-piperaquine on reducing malaria burden in school-aged children in Tanzania: methodology, challenges, and mitigation.
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Makenga G, Seth MD, Baraka V, Mmbando BP, Challe DP, Francis F, Mhina A, Minja DTR, Chiduo M, Mandara C, Liheluka E, Gesase S, Segeja M, Mtove G, Kamugisha M, Lusasi A, Chacky F, David A, Thawer S, Mohamed A, Lazaro S, Molteni F, Nkayamba A, Van Geertruyden JP, and Lusingu JPA
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- Humans, Child, Tanzania epidemiology, Drug Combinations, Antimalarials therapeutic use, Malaria epidemiology, Malaria prevention & control, Malaria drug therapy, Quinolines therapeutic use
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Background: It has been more than 20 years since the malaria epidemiologic shift to school-aged children was noted. In the meantime, school-aged children (5-15 years) have become increasingly more vulnerable with asymptomatic malaria prevalence reaching up to 70%, making them reservoirs for subsequent transmission of malaria in the endemic communities. Intermittent Preventive Treatment of malaria in schoolchildren (IPTsc) has proven to be an effective tool to shrink this reservoir. As of 3
rd June 2022, the World Health Organization recommends IPTsc in moderate and high endemic areas. Even so, for decision-makers, the adoption of scientific research recommendations has been stifled by real-world implementation challenges. This study presents methodology, challenges faced, and mitigations used in the evaluation of the implementation of IPTsc using dihydroartemisinin-piperaquine (DP) in three councils (Handeni District Council (DC), Handeni Town Council (TC) and Kilindi DC) of Tanga Region, Tanzania so as to understand the operational feasibility and effectiveness of IPTsc on malaria parasitaemia and clinical malaria incidence., Methods: The study deployed an effectiveness-implementation hybrid design to assess feasibility and effectiveness of IPTsc using DP, the interventional drug, against standard of care (control). Wards in the three study councils were the randomization unit (clusters). Each ward was randomized to implement IPTsc or not (control). In all wards in the IPTsc arm, DP was given to schoolchildren three times a year in four-month intervals. In each council, 24 randomly selected wards (12 per study arm, one school per ward) were chosen as representatives for intervention impact evaluation. Mixed design methods were used to assess the feasibility and acceptability of implementing IPTsc as part of a more comprehensive health package for schoolchildren. The study reimagined an existing school health programme for Neglected Tropical Diseases (NTD) control include IPTsc implementation., Results: The study shows IPTsc can feasibly be implemented by integrating it into existing school health and education systems, paving the way for sustainable programme adoption in a cost-effective manner., Conclusions: Through this article other interested countries may realise a feasible plan for IPTsc implementation. Mitigation to any challenge can be customized based on local circumstances without jeopardising the gains expected from an IPTsc programme. Trial registration clinicaltrials.gov, NCT04245033. Registered 28 January 2020, https://clinicaltrials.gov/ct2/show/NCT04245033., (© 2023. The Author(s).)- Published
- 2023
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8. Seroprevalence of SARS-CoV-2 antibodies among children and adolescents recruited in a malariometric survey in north-eastern Tanzania July 2021.
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Lyimo E, Fougeroux C, Malabeja A, Mbwana J, Hayuma PM, Liheluka E, Turner L, Gesase S, Lavstsen T, Lusingu JPA, Minja DTR, and Wang CW
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- Adolescent, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Young Adult, Antigens, Protozoan, Immunoglobulin G, Pandemics, SARS-CoV-2, Seroepidemiologic Studies, Tanzania epidemiology, Antibodies, Viral blood, COVID-19 epidemiology, Malaria, Falciparum epidemiology
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Background: African countries stand out globally as the region seemingly least affected by the COVID-19 pandemic, caused by the virus SARS-CoV-2. Besides a younger population and potential pre-existing immunity to a SARS-CoV-2-like virus, it has been hypothesized that co-infection or recent history of Plasmodium falciparum malaria may be protective of COVID-19 severity and mortality. The number of COVID-19 cases and deaths, however, may be vastly undercounted. Very little is known about the extent to which the Tanzanian population has been exposed to SARS-CoV-2. Here, we investigated the seroprevalence of IgG to SARS-CoV-2 spike protein in two Tanzanian rural communities 1½ years into the pandemic and the association of coinciding malaria infection and exposure., Methods: During a malariometric survey in July 2021 in two villages in north-eastern Tanzania, blood samples were taken from 501 participants (0-19 years old). Malaria was detected by mRDT and microscopy. Levels of IgG against the spike protein of SARS-CoV-2 were measured by ELISA as well as IgG against five different antigens of P. falciparum; CIDRα1.1, CIDRα1.4 and CIDRα1.5 of PfEMP1 and GLURP and MSP3., Results: The seroprevalence of SARS-CoV-2 IgG was 39.7% (106/267) in Kwamasimba and 32.5% (76/234) in Mkokola. In both villages the odds of being seropositive increased significantly with age (AOR = 1.12, 95% CI 1.07-1.17, p < 0.001). P. falciparum malaria prevalence by blood smear microscopy was 7.9% in Kwamasimba and 2.1% in Mkokola. 81.3% and 70.5% in Kwamasimba and Mkokola, respectively, showed recognition of minimum one malaria antigen. Residing in Kwamasimba was associated with a broader recognition (AOR = 1.91, 95% CI 1.34-2.71, p < 0.001). The recognition of malaria antigens increased significantly with age in both villages (AOR = 1.12; 95% CI 1.08-1.16, p < 0.001). Being SARS-CoV-2 seropositive did not associate with the breadth of malaria antigen recognition when adjusting for age (AOR = 0.99; 95% CI 0.83-1.18; p = 0.91)., Conclusion: More than a third of the children and adolescents in two rural communities in Tanzania had antibodies to SARS-CoV-2. In particular, the adolescents were seropositive but being seropositive did not associate with the status of coinciding malaria infections or previous exposure. In Tanzania, natural immunity may have developed fast, potentially protecting a substantial part of the population from later variants., (© 2022. The Author(s).)
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- 2022
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9. Prevalence of asymptomatic malaria, submicroscopic parasitaemia and anaemia in Korogwe District, north-eastern Tanzania.
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Hayuma PM, Wang CW, Liheluka E, Baraka V, Madebe RA, Minja DTR, Misinzo G, Alifrangis M, and Lusingu JPA
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- Adolescent, Anemia parasitology, Asymptomatic Infections epidemiology, Child, Child, Preschool, Cross-Sectional Studies, Female, Humans, Infant, Infant, Newborn, Malaria, Falciparum parasitology, Male, Parasitemia parasitology, Tanzania epidemiology, Young Adult, Anemia epidemiology, Malaria, Falciparum epidemiology, Parasitemia epidemiology, Plasmodium falciparum isolation & purification
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Background: Asymptomatic malaria infections largely remain undetected and act as a reservoir for continuous transmission. The study assessed the prevalence of submicroscopic asymptomatic malaria infections and anaemia in two rural low (300 m above sea level) and highland (700 m asl) settings of Korogwe District north-eastern Tanzania., Methods: A cross-sectional malariometric survey involving individuals aged 0-19 years was conducted in June 2018 in the two rural villages. Venous blood was collected from eligible study participants for estimation of haemoglobin level, detection of malaria by rapid diagnostic test (RDT), quantification of malaria parasitaemia by microscopy, as well as dried blood spot (DBS) for determining submicroscopic infections by PCR targeting the small subunit of the ribosomal ribonucleic acid (ssrRNA) of human Plasmodium., Results: Out of 565 individuals tested, 211 (37.3%) were malaria positive based on RDT, whereas only 81 (14.3%) were positive by microscopy. There was no significant difference in the prevalence between the highland and the lowland village, p = 0.19 and p = 0.78 microscopy and RDT, respectively. Three out of 206 (1.5%) RDT/microscopy negative samples were P. falciparum positive by PCR. Of the 211 RDT and 81 microscopy positive, 130 (61.6%) and 33 (40.7%), respectively, were defined as being asymptomatic. Of the 565 individuals, 135 (23.9%) were anaemic (haemoglobin < 11 g/dL) out of which 5.2% were severely anaemic. The risk of being anaemic was significantly higher among individuals with asymptomatic malaria as compared to those without malaria as confirmed by RDT (AOR = 2.06 (95% CI 1.32-3.20) while based on microscopic results there was no significant differences observed (AOR = 2.09, 95% CI 0.98-4.47). Age and altitude had no effect on the risk of anaemia even after adjusting for asymptomatic malaria., Conclusions: Asymptomatic malaria is associated with an increased risk of having anaemia in the study communities. The findings highlight the need for targeted interventions focusing on asymptomatic infections which is an important risks factor for anaemia in the community and act as a source of continued transmission of malaria in the study area., (© 2021. The Author(s).)
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- 2021
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10. Long-term incidence of severe malaria following RTS,S/AS01 vaccination in children and infants in Africa: an open-label 3-year extension study of a phase 3 randomised controlled trial.
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Tinto H, Otieno W, Gesase S, Sorgho H, Otieno L, Liheluka E, Valéa I, Sing'oei V, Malabeja A, Valia D, Wangwe A, Gvozdenovic E, Guerra Mendoza Y, Jongert E, Lievens M, Roman F, Schuerman L, and Lusingu J
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- Africa epidemiology, Child, Child, Preschool, Female, Humans, Incidence, Infant, Malaria Vaccines immunology, Male, Malaria epidemiology, Malaria Vaccines administration & dosage, Severity of Illness Index, Vaccination
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Background: Results from a previous phase 3 study showed efficacy of the RTS,S/AS01 vaccine against severe and clinical malaria in children (in 11 sites in Africa) during a 3-4-year follow-up. We aimed to investigate malaria incidence up to 7 years postvaccination in three of the sites of the initial study., Methods: In the initial phase 3 study, infants aged 6-12 weeks and children aged 5-17 months were randomly assigned (1:1:1) to receive four RTS,S/AS01 doses (four-dose group), three RTS,S/AS01 doses and a comparator dose (three-dose group), or four comparator doses (control group). In this open-label extension study in Korogwe (Tanzania), Kombewa (Kenya), and Nanoro (Burkina Faso), we assessed severe malaria incidences as the primary outcome for 3 additional years (January, 2014, to December, 2016), up to 6 years (younger children) or 7 years (older children) postprimary vaccination in the modified intention-to-treat population (ie, participants who received at least one dose of the study vaccine). As secondary outcomes, we evaluated clinical malaria incidences and serious adverse events. This trial is registered with ClinicalTrials.gov, number NCT02207816., Findings: We enrolled 1739 older children (aged 5-7 years) and 1345 younger children (aged 3-5 years). During the 3-year extension, 66 severe malaria cases were reported, resulting in severe malaria incidence of 0·004 cases per person-years at risk (PPY; 95% CI 0-0·033) in the four-dose group, 0·007 PPY (0·001-0·052) in the three-dose group, and 0·009 PPY (0·001-0·066) in the control group in the older children category and a vaccine efficacy against severe malaria that did not contribute significantly to the overall efficacy (four-dose group 53·7% [95% CI -13·7 to 81·1], p=0·093; three-dose group 23·3% [-67·1 to 64·8], p=0·50). In younger children, severe malaria incidences were 0·007 PPY (0·001-0·058) in the four-dose group, 0·007 PPY (0·001-0·054) in the three-dose group, and 0·011 PPY (0·001-0·083) in the control group. Vaccine efficacy against severe malaria also did not contribute significantly to the overall efficacy (four-dose group 32·1% [-53·1 to 69·9], p=0·35; three-dose group 37·6% [-44·4 to 73·0], p=0·27). Malaria transmission was still occurring as evidenced by an incidence of clinical malaria ranging from 0·165 PPY to 3·124 PPY across all study groups and sites. In older children, clinical malaria incidence was 1·079 PPY (95% CI 0·152-7·662) in the four-dose group, 1·108 PPY (0·156-7·868) in the three-dose group, and 1·016 PPY (0·14-7·213) in the control group. In younger children, malaria incidence was 1·632 PPY (0·23-11·59), 1·563 PPY (0·22-11·104), and 1·686 PPY (0·237-11·974), respectively. In the older age category in Nanoro, clinical malaria incidence was higher in the four-dose (2·444 PPY; p=0·011) and three-dose (2·411 PPY; p=0·034) groups compared with the control group (1·998 PPY). Three cerebral malaria episodes and five meningitis cases, but no vaccine-related severe adverse events, were reported., Interpretation: Overall, severe malaria incidence was low in all groups, with no evidence of rebound in RTS,S/AS01 recipients, despite an increased incidence of clinical malaria in older children who received RTS,S/AS01 compared with the comparator group in Nanoro. No safety signal was identified., Funding: GlaxoSmithKline Biologicals SA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
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- 2019
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11. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.
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Agnandji ST, Lell B, Fernandes JF, Abossolo BP, Methogo BG, Kabwende AL, Adegnika AA, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Machevo S, Acacio S, Bulo H, Sigauque B, Macete E, Alonso P, Abdulla S, Salim N, Minja R, Mpina M, Ahmed S, Ali AM, Mtoro AT, Hamad AS, Mutani P, Tanner M, Tinto H, D'Alessandro U, Sorgho H, Valea I, Bihoun B, Guiraud I, Kaboré B, Sombié O, Guiguemdé RT, Ouédraogo JB, Hamel MJ, Kariuki S, Oneko M, Odero C, Otieno K, Awino N, McMorrow M, Muturi-Kioi V, Laserson KF, Slutsker L, Otieno W, Otieno L, Otsyula N, Gondi S, Otieno A, Owira V, Oguk E, Odongo G, Woods JB, Ogutu B, Njuguna P, Chilengi R, Akoo P, Kerubo C, Maingi C, Lang T, Olotu A, Bejon P, Marsh K, Mwambingu G, Owusu-Agyei S, Asante KP, Osei-Kwakye K, Boahen O, Dosoo D, Asante I, Adjei G, Kwara E, Chandramohan D, Greenwood B, Lusingu J, Gesase S, Malabeja A, Abdul O, Mahende C, Liheluka E, Malle L, Lemnge M, Theander TG, Drakeley C, Ansong D, Agbenyega T, Adjei S, Boateng HO, Rettig T, Bawa J, Sylverken J, Sambian D, Sarfo A, Agyekum A, Martinson F, Hoffman I, Mvalo T, Kamthunzi P, Nkomo R, Tembo T, Tegha G, Tsidya M, Kilembe J, Chawinga C, Ballou WR, Cohen J, Guerra Y, Jongert E, Lapierre D, Leach A, Lievens M, Ofori-Anyinam O, Olivier A, Vekemans J, Carter T, Kaslow D, Leboulleux D, Loucq C, Radford A, Savarese B, Schellenberg D, Sillman M, and Vansadia P
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- Africa, Female, Humans, Immunization Schedule, Incidence, Infant, Intention to Treat Analysis, Malaria, Falciparum epidemiology, Male, Plasmodium falciparum immunology, Proportional Hazards Models, Treatment Outcome, Malaria Vaccines adverse effects, Malaria Vaccines immunology, Malaria, Falciparum prevention & control, Vaccines, Synthetic adverse effects, Vaccines, Synthetic immunology
- Abstract
Background: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial., Methods: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed., Results: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222)., Conclusions: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).
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- 2012
- Full Text
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12. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.
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Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Methogo BG, Doucka Y, Flamen A, Mordmüller B, Issifou S, Kremsner PG, Sacarlal J, Aide P, Lanaspa M, Aponte JJ, Nhamuave A, Quelhas D, Bassat Q, Mandjate S, Macete E, Alonso P, Abdulla S, Salim N, Juma O, Shomari M, Shubis K, Machera F, Hamad AS, Minja R, Mtoro A, Sykes A, Ahmed S, Urassa AM, Ali AM, Mwangoka G, Tanner M, Tinto H, D'Alessandro U, Sorgho H, Valea I, Tahita MC, Kaboré W, Ouédraogo S, Sandrine Y, Guiguemdé RT, Ouédraogo JB, Hamel MJ, Kariuki S, Odero C, Oneko M, Otieno K, Awino N, Omoto J, Williamson J, Muturi-Kioi V, Laserson KF, Slutsker L, Otieno W, Otieno L, Nekoye O, Gondi S, Otieno A, Ogutu B, Wasuna R, Owira V, Jones D, Onyango AA, Njuguna P, Chilengi R, Akoo P, Kerubo C, Gitaka J, Maingi C, Lang T, Olotu A, Tsofa B, Bejon P, Peshu N, Marsh K, Owusu-Agyei S, Asante KP, Osei-Kwakye K, Boahen O, Ayamba S, Kayan K, Owusu-Ofori R, Dosoo D, Asante I, Adjei G, Adjei G, Chandramohan D, Greenwood B, Lusingu J, Gesase S, Malabeja A, Abdul O, Kilavo H, Mahende C, Liheluka E, Lemnge M, Theander T, Drakeley C, Ansong D, Agbenyega T, Adjei S, Boateng HO, Rettig T, Bawa J, Sylverken J, Sambian D, Agyekum A, Owusu L, Martinson F, Hoffman I, Mvalo T, Kamthunzi P, Nkomo R, Msika A, Jumbe A, Chome N, Nyakuipa D, Chintedza J, Ballou WR, Bruls M, Cohen J, Guerra Y, Jongert E, Lapierre D, Leach A, Lievens M, Ofori-Anyinam O, Vekemans J, Carter T, Leboulleux D, Loucq C, Radford A, Savarese B, Schellenberg D, Sillman M, and Vansadia P
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- Africa, Age Factors, Double-Blind Method, Female, Follow-Up Studies, Humans, Incidence, Infant, Intention to Treat Analysis, Malaria, Falciparum epidemiology, Malaria, Falciparum parasitology, Male, Meningitis epidemiology, Meningitis etiology, Parasite Load, Seizures epidemiology, Seizures etiology, Treatment Outcome, Malaria Vaccines adverse effects, Malaria Vaccines immunology, Malaria, Falciparum prevention & control, Plasmodium falciparum immunology, Plasmodium falciparum isolation & purification
- Abstract
Background: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries., Methods: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories., Results: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64)., Conclusions: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).
- Published
- 2011
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