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1.
Nat Immunol ; 22(3): 287-300, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33574617

RESUMEN

Sub-Saharan Africa currently experiences an unprecedented wave of urbanization, which has important consequences for health and disease patterns. This study aimed to investigate and integrate the immune and metabolic consequences of rural or urban lifestyles and the role of nutritional changes associated with urban living. In a cohort of 323 healthy Tanzanians, urban as compared to rural living was associated with a pro-inflammatory immune phenotype, both at the transcript and protein levels. We identified different food-derived and endogenous circulating metabolites accounting for these differences. Serum from urban dwellers induced reprogramming of innate immune cells with higher tumor necrosis factor production upon microbial re-stimulation in an in vitro model of trained immunity. These data demonstrate important shifts toward an inflammatory phenotype associated with an urban lifestyle and provide new insights into the underlying dietary and metabolic factors, which may affect disease epidemiology in sub-Sahara African countries.


Asunto(s)
Citocinas/sangre , Dieta Saludable , Metabolismo Energético , Inmunidad Innata , Mediadores de Inflamación/sangre , Salud Rural , Salud Urbana , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Citocinas/genética , Metabolismo Energético/genética , Femenino , Humanos , Inmunidad Innata/genética , Masculino , Metaboloma , Persona de Mediana Edad , Estado Nutricional , Valor Nutritivo , Conducta de Reducción del Riesgo , Estaciones del Año , Tanzanía , Transcriptoma , Factor de Necrosis Tumoral alfa/sangre , Urbanización , Adulto Joven
2.
Nature ; 625(7996): 813-821, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38172637

RESUMEN

Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established1-6, little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated that other ABO-associated species can also utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc utilization genes are also associated with the host's cardiometabolic health, particularly in individuals with mucosal A-antigen. Together, the findings of our study demonstrate that genetic associations across the human genome and bacterial metagenome can provide functional insights into the reciprocal host-microbiome relationship.


Asunto(s)
Bacterias , Microbioma Gastrointestinal , Interacciones Microbiota-Huesped , Metagenoma , Humanos , Acetilgalactosamina/metabolismo , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Estudios de Cohortes , Simulación por Computador , Faecalibacterium prausnitzii/genética , Microbioma Gastrointestinal/genética , Genoma Humano/genética , Genotipo , Interacciones Microbiota-Huesped/genética , Técnicas In Vitro , Metagenoma/genética , Familia de Multigenes , Países Bajos , Tanzanía
3.
Nature ; 615(7954): 866-873, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36991187

RESUMEN

The urban peoples of the Swahili coast traded across eastern Africa and the Indian Ocean and were among the first practitioners of Islam among sub-Saharan people1,2. The extent to which these early interactions between Africans and non-Africans were accompanied by genetic exchange remains unknown. Here we report ancient DNA data for 80 individuals from 6 medieval and early modern (AD 1250-1800) coastal towns and an inland town after AD 1650. More than half of the DNA of many of the individuals from coastal towns originates from primarily female ancestors from Africa, with a large proportion-and occasionally more than half-of the DNA coming from Asian ancestors. The Asian ancestry includes components associated with Persia and India, with 80-90% of the Asian DNA originating from Persian men. Peoples of African and Asian origins began to mix by about AD 1000, coinciding with the large-scale adoption of Islam. Before about AD 1500, the Southwest Asian ancestry was mainly Persian-related, consistent with the narrative of the Kilwa Chronicle, the oldest history told by people of the Swahili coast3. After this time, the sources of DNA became increasingly Arabian, consistent with evidence of growing interactions with southern Arabia4. Subsequent interactions with Asian and African people further changed the ancestry of present-day people of the Swahili coast in relation to the medieval individuals whose DNA we sequenced.


Asunto(s)
Pueblo Africano , Asiático , Genética de Población , Femenino , Humanos , Masculino , Pueblo Africano/genética , Asiático/genética , Historia Medieval , Océano Índico , Tanzanía , Kenia , Mozambique , Comoras , Historia del Siglo XV , Historia del Siglo XVI , Historia del Siglo XVII , India/etnología , Persia/etnología , Arabia/etnología , ADN Antiguo/análisis
4.
Nature ; 620(7973): 336-343, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37558848

RESUMEN

Anthropogenic climate change is predicted to severely impact the global hydrological cycle1, particularly in tropical regions where agriculture-based economies depend on monsoon rainfall2. In the Horn of Africa, more frequent drought conditions in recent decades3,4 contrast with climate models projecting precipitation to increase with rising temperature5. Here we use organic geochemical climate-proxy data from the sediment record of Lake Chala (Kenya and Tanzania) to probe the stability of the link between hydroclimate and temperature over approximately the past 75,000 years, hence encompassing a sufficiently wide range of temperatures to test the 'dry gets drier, wet gets wetter' paradigm6 of anthropogenic climate change in the time domain. We show that the positive relationship between effective moisture and temperature in easternmost Africa during the cooler last glacial period shifted to negative around the onset of the Holocene 11,700 years ago, when the atmospheric carbon dioxide concentration exceeded 250 parts per million and mean annual temperature approached modern-day values. Thus, at that time, the budget between monsoonal precipitation and continental evaporation7 crossed a tipping point such that the positive influence of temperature on evaporation became greater than its positive influence on precipitation. Our results imply that under continued anthropogenic warming, the Horn of Africa will probably experience further drying, and they highlight the need for improved simulation of both dynamic and thermodynamic processes in the tropical hydrological cycle.


Asunto(s)
Cambio Climático , Modelos Climáticos , Sequías , Lluvia , Temperatura , Ciclo Hidrológico , Agua , Atmósfera/química , Dióxido de Carbono/análisis , Cambio Climático/historia , Sequías/estadística & datos numéricos , Sedimentos Geológicos/química , Historia Antigua , Humedad , Kenia , Lagos/química , Tanzanía , Termodinámica , Clima Tropical , Volatilización , Agua/análisis
5.
Am J Hum Genet ; 111(5): 927-938, 2024 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-38701745

RESUMEN

Leukocyte telomere length (LTL) varies significantly across human populations, with individuals of African ancestry having longer LTL than non-Africans. However, the genetic and environmental drivers of LTL variation in Africans remain largely unknown. We report here on the relationship between LTL, genetics, and a variety of environmental and climatic factors in ethnically diverse African adults (n = 1,818) originating from Botswana, Tanzania, Ethiopia, and Cameroon. We observe significant variation in LTL among populations, finding that the San hunter-gatherers from Botswana have the longest leukocyte telomeres and that the Fulani pastoralists from Cameroon have the shortest telomeres. Genetic factors explain ∼50% of LTL variation among individuals. Moreover, we observe a significant negative association between Plasmodium falciparum malaria endemicity and LTL while adjusting for age, sex, and genetics. Within Africa, adults from populations indigenous to areas with high malaria exposure have shorter LTL than those in populations indigenous to areas with low malaria exposure. Finally, we explore to what degree the genetic architecture underlying LTL in Africa covaries with malaria exposure.


Asunto(s)
Malaria Falciparum , Telómero , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , África del Sur del Sahara/epidemiología , Población Negra/etnología , Población Negra/genética , Enfermedades Endémicas , Leucocitos/metabolismo , Malaria Falciparum/genética , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Plasmodium falciparum/patogenicidad , Pueblo Africano Subsahariano , Telómero/genética , Homeostasis del Telómero/genética , Botswana , Tanzanía , Camerún , Pueblo del Sur de África
6.
Nature ; 600(7889): 468-471, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34853470

RESUMEN

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.


Asunto(s)
Pie/anatomía & histología , Pie/fisiología , Fósiles , Marcha/fisiología , Hominidae/clasificación , Hominidae/fisiología , Animales , Archivos , Femenino , Hominidae/anatomía & histología , Humanos , Imagenología Tridimensional , Rayos Láser , Masculino , Modelos Biológicos , Pan troglodytes/anatomía & histología , Pan troglodytes/fisiología , Fotogrametría , Filogenia , Tanzanía , Ursidae/anatomía & histología , Ursidae/fisiología
7.
Nature ; 582(7810): 104-108, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32427965

RESUMEN

Malaria caused by Plasmodium falciparum remains the leading single-agent cause of mortality in children1, yet the promise of an effective vaccine has not been fulfilled. Here, using our previously described differential screening method to analyse the proteome of blood-stage P. falciparum parasites2, we identify P. falciparum glutamic-acid-rich protein (PfGARP) as a parasite antigen that is recognized by antibodies in the plasma of children who are relatively resistant-but not those who are susceptible-to malaria caused by P. falciparum. PfGARP is a parasite antigen of 80 kDa that is expressed on the exofacial surface of erythrocytes infected by early-to-late-trophozoite-stage parasites. We demonstrate that antibodies against PfGARP kill trophozoite-infected erythrocytes in culture by inducing programmed cell death in the parasites, and that vaccinating non-human primates with PfGARP partially protects against a challenge with P. falciparum. Furthermore, our longitudinal cohort studies showed that, compared to individuals who had naturally occurring anti-PfGARP antibodies, Tanzanian children without anti-PfGARP antibodies had a 2.5-fold-higher risk of severe malaria and Kenyan adolescents and adults without these antibodies had a twofold-higher parasite density. By killing trophozoite-infected erythrocytes, PfGARP could synergize with other vaccines that target parasite invasion of hepatocytes or the invasion of and egress from erythrocytes.


Asunto(s)
Apoptosis/inmunología , Péptidos y Proteínas de Señalización Intercelular/inmunología , Malaria Falciparum/inmunología , Malaria Falciparum/prevención & control , Parásitos/inmunología , Plasmodium falciparum/citología , Plasmodium falciparum/inmunología , Proteínas Protozoarias/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/química , Antígenos de Protozoos/inmunología , Aotidae/inmunología , Aotidae/parasitología , Caspasas/metabolismo , Niño , Estudios de Cohortes , ADN Protozoario/química , ADN Protozoario/metabolismo , Activación Enzimática , Eritrocitos/parasitología , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/química , Kenia , Vacunas contra la Malaria/inmunología , Malaria Falciparum/parasitología , Masculino , Ratones , Parásitos/citología , Parásitos/crecimiento & desarrollo , Plasmodium falciparum/crecimiento & desarrollo , Proteínas Protozoarias/química , Tanzanía , Trofozoítos/citología , Trofozoítos/crecimiento & desarrollo , Trofozoítos/inmunología , Vacuolas/inmunología
8.
Proc Natl Acad Sci U S A ; 120(32): e2207398120, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37523529

RESUMEN

Land inequality stalls economic development, entrenches poverty, and is associated with environmental degradation. Yet, rigorous assessments of land-use interventions attend to inequality only rarely. A land inequality lens is especially important to understand how recent large-scale land acquisitions (LSLAs) affect smallholder and indigenous communities across as much as 100 million hectares around the world. This paper studies inequalities in land assets, specifically landholdings and farm size, to derive insights into the distributional outcomes of LSLAs. Using a household survey covering four pairs of land acquisition and control sites in Tanzania, we use a quasi-experimental design to characterize changes in land inequality and subsequent impacts on well-being. We find convincing evidence that LSLAs in Tanzania lead to both reduced landholdings and greater farmland inequality among smallholders. Households in proximity to LSLAs are associated with 21.1% (P = 0.02) smaller landholdings while evidence, although insignificant, is suggestive that farm sizes are also declining. Aggregate estimates, however, hide that households in the bottom quartiles of farm size suffer the brunt of landlessness and land loss induced by LSLAs that combine to generate greater farmland inequality. Additional analyses find that land inequality is not offset by improvements in other livelihood dimensions, rather farm size decreases among households near LSLAs are associated with no income improvements, lower wealth, increased poverty, and higher food insecurity. The results demonstrate that without explicit consideration of distributional outcomes, land-use policies can systematically reinforce existing inequalities.


Asunto(s)
Agricultura , Renta , Granjas , Tanzanía , Composición Familiar
9.
Proc Natl Acad Sci U S A ; 120(2): e2211055120, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36595676

RESUMEN

Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, Plasmodium falciparum, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of P. falciparum infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative P. falciparum exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime P. falciparum infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual P. falciparum infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to P. falciparum malaria and support emphasizing the link between malaria and eBL.


Asunto(s)
Linfoma de Burkitt , Malaria Falciparum , Malaria , Humanos , Linfoma de Burkitt/epidemiología , Linfoma de Burkitt/genética , Plasmodium falciparum , Estudios de Casos y Controles , Uganda/epidemiología , Kenia/epidemiología , Tanzanía/epidemiología , Estudios Transversales , Malaria Falciparum/complicaciones , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Malaria/epidemiología
10.
Mol Biol Evol ; 41(7)2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38865496

RESUMEN

Cichlid fishes of the genus Oreochromis (tilapia) are among the most important fish for inland capture fisheries and global aquaculture. Deliberate introductions of non-native species for fisheries improvement and accidental escapees from farms have resulted in admixture with indigenous species. Such hybridization may be detrimental to native biodiversity, potentially leading to genomic homogenization of populations and the loss of important genetic material associated with local adaptation. By contrast, introgression may fuel diversification when combined with ecological opportunity, by supplying novel genetic combinations. To date, the role of introgression in the evolutionary history of tilapia has not been explored. Here we studied both ancient and recent hybridization in tilapia, using whole genome resequencing of 575 individuals from 23 species. We focused on Tanzania, a natural hotspot of tilapia diversity, and a country where hybridization between exotic and native species in the natural environment has been previously reported. We reconstruct the first genome-scale phylogeny of the genus and reveal prevalent ancient gene flow across the Oreochromis phylogeny. This has likely resulted in the hybrid speciation of one species, O. chungruruensis. We identify multiple cases of recent hybridization between native and introduced species in the wild, linked to the use of non-native species in both capture fisheries improvement and aquaculture. This has potential implications for both conservation of wild populations and the development of the global tilapia aquaculture industry.


Asunto(s)
Hibridación Genética , Filogenia , Animales , Tanzanía , Flujo Génico , Cíclidos/genética , Tilapia/genética
11.
Am J Hum Genet ; 109(3): 471-485, 2022 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-35167808

RESUMEN

Humans exhibit remarkable interindividual and interpopulation immune response variability upon microbial challenges. Cytokines play a vital role in regulating inflammation and immune responses, but dysregulation of cytokine responses has been implicated in different disease states. Host genetic factors were previously shown to significantly impact cytokine response heterogeneity mainly in European-based studies, but it is unclear whether these findings are transferable to non-European individuals. Here, we aimed to identify genetic variants modulating cytokine responses in healthy adults of East African ancestry from Tanzania. We leveraged both cytokine and genetic data and performed genome-wide cytokine quantitative trait loci (cQTLs) mapping. The results were compared with another cohort of healthy adults of Western European ancestry via direct overlap and functional enrichment analyses. We also performed meta-analyses to identify cQTLs with congruent effect direction in both populations. In the Tanzanians, cQTL mapping identified 80 independent suggestive loci and one genome-wide significant locus (TBC1D22A) at chromosome 22; SNP rs12169244 was associated with IL-1b release after Salmonella enteritidis stimulation. Remarkably, the identified cQTLs varied significantly when compared to the European cohort, and there was a very limited percentage of overlap (1.6% to 1.9%). We further observed ancestry-specific pathways regulating induced cytokine responses, and there was significant enrichment of the interferon pathway specifically in the Tanzanians. Furthermore, contrary to the Europeans, genetic variants in the TLR10-TLR1-TLR6 locus showed no effect on cytokine response. Our data reveal both ancestry-specific effects of genetic variants and pathways on cytokine response heterogeneity, hence arguing for the importance of initiatives to include diverse populations into genomics research.


Asunto(s)
Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Adulto , Citocinas/genética , Predisposición Genética a la Enfermedad , Genómica , Humanos , Polimorfismo de Nucleótido Simple/genética , Tanzanía
12.
Lancet ; 404(10453): 683-691, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153818

RESUMEN

BACKGROUND: Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections. METHODS: We conducted a double-blind, superiority, phase 2b, randomised controlled clinical trial comparing emodepside and albendazole. Participants in the emodepside group received six 5 mg tablets of emodepside (totalling 30 mg) and one placebo; participants in the albendazole group received one 400 mg tablet of albendazole and six placebos. Participants were recruited from four endemic villages and three secondary schools in Pemba Island, Tanzania. Participants aged 12-60 years were eligible for treatment if they were positive for hookworm infection, and they had 48 or more eggs per gram from four Kato-Katz thick smears and at least two slides had more than one hookworm egg present. Participants' treatment allocation was stratified by infection intensity and efficacy was measured by cure rate: participants who were hookworm positive and became hookworm negative after treatment. Adverse events were reported at 3 h, 24 h, 48 h, and 14-21 days post-treatment. The trial is registered at ClinicalTrials.gov, NCT05538767. FINDINGS: From Sept 15 to Nov 8, 2022, and from Feb 15 to March 15, 2023, 1609 individuals were screened for hookworm. Of these, 293 individuals were treated: 147 with albendazole and 146 with emodepside. Emodepside demonstrated superiority, with an observed cure rate against hookworm of 96·6%, which was significantly higher compared with albendazole (cure rate 81·2%, odds ratio 0·14, 95% CI 0·04-0·35; p=0·0001). The most common adverse event in the emodepside treatment group was vision blur at 3 h after treatment (57 [39%] of 146). Other common adverse events were vision blur at 24 h after treatment (55 [38%]), and headache and dizziness at 3 h after treatment (55 [38%] for headache and 43 [30%] for dizziness). In the emodepside treatment group, 298 (93%) of the 319 adverse events were mild. The most commonly reported adverse events in the albendazole treatment group were headache and dizziness at 3 h after treatment (27 [18%] of 147 for headache and 14 [10%] for dizziness). No serious adverse events were reported. INTERPRETATION: This phase 2b clinical trial confirms the high efficacy of emodepside against hookworm infections, solidifying emodepside as a promising anthelmintic candidate. However, although the observed safety events were generally mild in severity, considerations must be made to balance the strong efficacy outcomes with the increased frequency of adverse events compared with albendazole. FUNDING: European Research Council.


Asunto(s)
Albendazol , Antihelmínticos , Depsipéptidos , Infecciones por Uncinaria , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Albendazol/uso terapéutico , Albendazol/efectos adversos , Antihelmínticos/efectos adversos , Antihelmínticos/uso terapéutico , Depsipéptidos/efectos adversos , Depsipéptidos/uso terapéutico , Método Doble Ciego , Infecciones por Uncinaria/tratamiento farmacológico , Tanzanía , Resultado del Tratamiento
13.
Lancet ; 404(10463): 1645-1656, 2024 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-39461792

RESUMEN

BACKGROUND: Tranexamic acid, given within 3 h of birth, reduces bleeding deaths in women with postpartum haemorrhage. We examined whether giving tranexamic acid shortly after birth can prevent postpartum haemorrhage in women with moderate or severe anaemia. METHODS: This international, randomised, double-blind, placebo-controlled trial was done in 34 hospitals across four countries (Nigeria, Pakistan, Tanzania, and Zambia). We recruited women of any age in active labour with moderate or severe anaemia (haemoglobin <100 g/L). We randomly assigned women (1:1) who had given birth vaginally to receive 1 g of tranexamic acid or matching placebo by slow intravenous injection (over 10 min) within 15 min of the umbilical cord being cut or clamped. Women were randomly assigned by selection of the lowest numbered treatment pack from a box containing 20 packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to group assignment. The primary outcome was a clinical diagnosis of primary postpartum haemorrhage, which might be an estimated blood loss of more than 500 mL or any blood loss sufficient to compromise haemodynamic stability within 24 h of randomisation, analysed on an intention-to-treat basis. Safety analyses were performed in all participants included in the intention-to-treat population. This trial was registered on ISRCTN (ISRCTN62396133), ClinicalTrials.gov (NCT03475342), and the Pan African Clinical Trial Registry (PACTR201909735842379) and is closed to recruitment. FINDINGS: From Aug 24, 2019, to Sept 19, 2023, 16 586 women aged 14-50 years were invited to take part and 1518 were excluded. 7580 women were randomly assigned to receive tranexamic acid and 7488 to receive placebo. Primary outcome data were unavailable for one woman in each group. The median time interval from the start of the administration of the trial treatment to the diagnosis of postpartum haemorrhage was 18·5 min (IQR 5-58); 20 min (8-64) in women with moderate anaemia and 13 min (7-44) in women with severe anaemia. 358 (35%) of 1024 with postpartum haemorrhage for whom time data were available were diagnosed before the trial treatment had been fully administered. Clinically diagnosed postpartum haemorrhage occurred in 530 (7·0%) of 7579 in the tranexamic acid group and in 497 (6·6%) of 7487 in the placebo group (risk ratio [RR] 1·05, 95% CI 0·94-1·19). There was no strong evidence against the null hypothesis of homogeneity of effects for any of the prespecified subgroup analyses: severity of anaemia (p=0·44), antepartum haemorrhage (p=0·044), birth canal trauma (p=0·37), use of pain control (p=0·37), and baseline risk of postpartum haemorrhage (p=0·31). There were no vascular occlusive events (pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction) reported in either group. There were no adverse events related to the treatment and no treatment-related deaths. INTERPRETATION: In women with moderate and severe anaemia, giving tranexamic acid within 15 min of the umbilical cord being clamped did not reduce the risk of clinically diagnosed postpartum haemorrhage. FUNDING: The Bill & Melinda Gates Foundation and the Wellcome Trust.


Asunto(s)
Anemia , Antifibrinolíticos , Hemorragia Posparto , Ácido Tranexámico , Humanos , Hemorragia Posparto/tratamiento farmacológico , Hemorragia Posparto/prevención & control , Femenino , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/administración & dosificación , Método Doble Ciego , Antifibrinolíticos/administración & dosificación , Antifibrinolíticos/uso terapéutico , Adulto , Embarazo , Anemia/tratamiento farmacológico , Tanzanía , Adulto Joven , Resultado del Tratamiento , Nigeria , Zambia , Pakistán
14.
N Engl J Med ; 386(5): 428-436, 2022 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-35108469

RESUMEN

BACKGROUND: It has been hypothesized that in high-transmission settings, malaria control in early childhood (<5 years of age) might delay the acquisition of functional immunity and shift child deaths from younger to older ages. METHODS: We used data from a 22-year prospective cohort study in rural southern Tanzania to estimate the association between early-life use of treated nets and survival to adulthood. All the children born between January 1, 1998, and August 30, 2000, in the study area were invited to enroll in a longitudinal study from 1998 through 2003. Adult survival outcomes were verified in 2019 through community outreach and mobile telephones. We used Cox proportional-hazards models to estimate the association between the use of treated nets in early childhood and survival to adulthood, adjusting for potential confounders. RESULTS: A total of 6706 children were enrolled. In 2019, we verified information on the vital status of 5983 participants (89%). According to reports of early-life community outreach visits, approximately one quarter of children never slept under a treated net, one half slept under a treated net some of the time, and the remaining quarter always slept under a treated net. Participants who were reported to have used treated nets at half the early-life visits or more had a hazard ratio for death of 0.57 (95% confidence interval [CI], 0.45 to 0.72) as compared with those who were reported to have used treated nets at less than half the visits. The corresponding hazard ratio between 5 years of age and adulthood was 0.93 (95% CI, 0.58 to 1.49). CONCLUSIONS: In this long-term study of early-life malaria control in a high-transmission setting, the survival benefit from early-life use of treated nets persisted to adulthood. (Funded by the Eckenstein-Geigy Professorship and others.).


Asunto(s)
Insecticidas , Malaria/prevención & control , Mosquiteros , Estudios de Cohortes , Femenino , Humanos , Lactante , Malaria/mortalidad , Masculino , Análisis de Supervivencia , Tanzanía/epidemiología
15.
PLoS Pathog ; 19(4): e1010893, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37014917

RESUMEN

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Tanzanía/epidemiología , Tuberculosis/epidemiología , Genotipo , Virulencia
16.
EMBO Rep ; 24(8): e57596, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37401864

RESUMEN

A severe outbreak of bacterial blight in East Africa has scientists puzzled about the origin of the pathogen and how to deal with it.


Asunto(s)
Oryza , Tanzanía/epidemiología , Enfermedades de las Plantas/microbiología
17.
Nature ; 568(7750): 88-92, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30918402

RESUMEN

Agriculture and the exploitation of natural resources have transformed tropical mountain ecosystems across the world, and the consequences of these transformations for biodiversity and ecosystem functioning are largely unknown1-3. Conclusions that are derived from studies in non-mountainous areas are not suitable for predicting the effects of land-use changes on tropical mountains because the climatic environment rapidly changes with elevation, which may mitigate or amplify the effects of land use4,5. It is of key importance to understand how the interplay of climate and land use constrains biodiversity and ecosystem functions to determine the consequences of global change for mountain ecosystems. Here we show that the interacting effects of climate and land use reshape elevational trends in biodiversity and ecosystem functions on Africa's largest mountain, Mount Kilimanjaro (Tanzania). We find that increasing land-use intensity causes larger losses of plant and animal species richness in the arid lowlands than in humid submontane and montane zones. Increases in land-use intensity are associated with significant changes in the composition of plant, animal and microorganism communities; stronger modifications of plant and animal communities occur in arid and humid ecosystems, respectively. Temperature, precipitation and land use jointly modulate soil properties, nutrient turnover, greenhouse gas emissions, plant biomass and productivity, as well as animal interactions. Our data suggest that the response of ecosystem functions to land-use intensity depends strongly on climate; more-severe changes in ecosystem functioning occur in the arid lowlands and the cold montane zone. Interactions between climate and land use explained-on average-54% of the variation in species richness, species composition and ecosystem functions, whereas only 30% of variation was related to single drivers. Our study reveals that climate can modulate the effects of land use on biodiversity and ecosystem functioning, and points to a lowered resistance of ecosystems in climatically challenging environments to ongoing land-use changes in tropical mountainous regions.


Asunto(s)
Agricultura/estadística & datos numéricos , Altitud , Biodiversidad , Ecosistema , Clima Tropical , Animales , Humedad , Microbiología , Plantas , Lluvia , Tanzanía , Temperatura
18.
Proc Natl Acad Sci U S A ; 119(10): e2112063119, 2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35238660

RESUMEN

SignificanceTwo billion people across the planet suffer from nutrient deficiencies. Dietary diversification is key to solving this problem, yet many food and nutrition security policies, especially in low- and middle-income countries, still focus on increasing agricultural production and access to sufficient calories as the main solution. But calories are not all equal. Here, we show how deforestation in Tanzania caused a reduction in fruit and vegetable consumption (of 14 g per person per day) and thus vitamin A adequacy of diets. Using a combination of regression and weighting analyses to generate quasi-experimental quantitative estimates of the impacts of deforestation on people's food intake, our study establishes a causal link between deforestation and people's dietary quality.


Asunto(s)
Ingestión de Energía , Conducta Alimentaria , Frutas , Población Rural , Verduras , Femenino , Humanos , Masculino , Tanzanía
19.
J Infect Dis ; 229(4): 959-968, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37992117

RESUMEN

BACKGROUND: Recent data indicate that non-Plasmodium falciparum species may be more prevalent than thought in sub-Saharan Africa. Although Plasmodium malariae, Plasmodium ovale spp., and Plasmodium vivax are less severe than P. falciparum, treatment and control are more challenging, and their geographic distributions are not well characterized. METHODS: We randomly selected 3284 of 12 845 samples collected from cross-sectional surveys in 100 health facilities across 10 regions of Mainland Tanzania and performed quantitative real-time PCR to determine presence and parasitemia of each malaria species. RESULTS: P. falciparum was most prevalent, but P. malariae and P. ovale were found in all but 1 region, with high levels (>5%) of P. ovale in 7 regions. The highest P. malariae positivity rate was 4.5% in Mara and 8 regions had positivity rates ≥1%. We only detected 3 P. vivax infections, all in Kilimanjaro. While most nonfalciparum malaria-positive samples were coinfected with P. falciparum, 23.6% (n = 13 of 55) of P. malariae and 14.7% (n = 24 of 163) of P. ovale spp. were monoinfections. CONCLUSIONS: P. falciparum remains by far the largest threat, but our data indicate that malaria elimination efforts in Tanzania will require increased surveillance and improved understanding of the biology of nonfalciparum species.


Asunto(s)
Malaria Falciparum , Malaria , Humanos , Tanzanía/epidemiología , Estudios Transversales , Malaria/epidemiología , Malaria Falciparum/epidemiología , Plasmodium malariae/genética
20.
J Infect Dis ; 230(2): 485-496, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38781438

RESUMEN

BACKGROUND: Asymptomatic carriage of malaria parasites persists even as malaria transmission declines. Low-density infections are often submicroscopic, not detected with rapid diagnostic tests (RDTs) or microscopy but detectable by polymerase chain reaction (PCR). METHODS: To characterize submicroscopic Plasmodium falciparum carriage in an area of declining malaria transmission, asymptomatic persons >5 years of age in rural Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir of infection across villages, determined factors associated with submicroscopic carriage, and assessed the natural history of submicroscopic malaria over 4 weeks. RESULTS: Among 6076 participants, P. falciparum prevalences by RDT, microscopy, and PCR were 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female sex, dry season months, screened windows, and bed net use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over 4 weeks, 23% of submicroscopic carriers (61 of 266) became RDT positive, with half exhibiting symptoms, while half (133 of 266) were no longer parasitemic at the end of 4 weeks. Progression to RDT-positive patent malaria occurred more frequently in villages with higher malaria prevalence. CONCLUSIONS: Microheterogeneity in transmission observed at the village level appears to affect both the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania.


Asunto(s)
Portador Sano , Malaria Falciparum , Plasmodium falciparum , Humanos , Tanzanía/epidemiología , Femenino , Malaria Falciparum/transmisión , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Masculino , Adulto , Adolescente , Plasmodium falciparum/genética , Plasmodium falciparum/aislamiento & purificación , Niño , Portador Sano/transmisión , Portador Sano/epidemiología , Portador Sano/parasitología , Adulto Joven , Preescolar , Prevalencia , Persona de Mediana Edad , Población Rural , Reacción en Cadena de la Polimerasa , Microscopía , Infecciones Asintomáticas/epidemiología , Anciano
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