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BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine. METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min. INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered. FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.
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Antimaláricos , Complicações Parasitárias na Gravidez , Quinolinas , Recém-Nascido , Gravidez , Feminino , Humanos , Adulto , Adulto Jovem , Pirimetamina/efeitos adversos , Sulfadoxina/efeitos adversos , Resultado da Gravidez , Antimaláricos/efeitos adversos , Azitromicina/efeitos adversos , Complicações Parasitárias na Gravidez/tratamento farmacológico , Complicações Parasitárias na Gravidez/prevenção & controle , Complicações Parasitárias na Gravidez/epidemiologia , Combinação de Medicamentos , Quênia , TanzâniaRESUMO
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.
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Diarreia , Febre , População Rural , Humanos , Tanzânia/epidemiologia , Estudos Transversais , Febre/tratamento farmacológico , Febre/terapia , Pré-Escolar , Diarreia/terapia , Diarreia/tratamento farmacológico , Feminino , Masculino , Lactente , Pais , Malária/tratamento farmacológico , Adulto , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.
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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 3rd 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.
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Antimaláricos , Malária , Quinolinas , Humanos , Criança , Antimaláricos/uso terapêutico , Tanzânia/epidemiologia , Malária/epidemiologia , Malária/prevenção & controle , Malária/tratamento farmacológico , Quinolinas/uso terapêutico , Combinação de MedicamentosRESUMO
OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.
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BACKGROUND: The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA. METHODS: Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003-2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age. Mixed-effects regression models were used to compare the association between malaria in pregnancy and SGA when using the STOPPAM and the Intergrowth-21 references, respectively. RESULTS: The 10th percentile for birthweights-for-gestational age was lower for STOPPAM than for Intergrowth-21, leading to a prevalence of SGASTOPPAM of 14.2% and SGAIG21 of 18.0%, p < 0.001. The association between malaria in pregnancy and SGA was stronger for STOPPAM (adjusted odds ratio (aOR) 1.30 [1.09-1.56], p < 0.01) than for Intergrowth-21 (aOR 1.19 [1.00-1.40], p = 0.04), particularly among paucigravidae (SGASTOPPAM aOR 1.36 [1.09-1.71], p < 0.01 vs SGAIG21 aOR 1.21 [0.97-1.50], p = 0.08). CONCLUSIONS: The prevalence of SGA may be overestimated and the impact of malaria in pregnancy underestimated when using Intergrowth-21. Comparing local reference charts to global references when assessing and interpreting the impact of malaria in pregnancy may be appropriate.
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Recém-Nascido Pequeno para a Idade Gestacional , Malária , Peso ao Nascer , Feminino , Retardo do Crescimento Fetal , Idade Gestacional , Humanos , Recém-Nascido , Malária/epidemiologia , Gravidez , Tanzânia/epidemiologiaRESUMO
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.
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Anticorpos Antivirais , COVID-19 , Malária Falciparum , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Adulto Jovem , Anticorpos Antivirais/sangue , Antígenos de Protozoários , COVID-19/epidemiologia , Imunoglobulina G , Malária Falciparum/epidemiologia , Pandemias , SARS-CoV-2 , Estudos Soroepidemiológicos , Tanzânia/epidemiologiaRESUMO
INTRODUCTION: Identification of low birthweight and small for gestational age is pivotal in clinical management and many research studies, but in low-income countries, birthweight is often unavailable within 24 h of birth. Newborn weights measured within days after birth and knowledge of the growth patterns in the first week of life can help estimate the weight at birth retrospectively. This study aimed to generate sex-specific prediction maps and weight reference charts for the retrospective estimation of birthweight for exclusively breastfed newborns in a low-resource setting. MATERIAL AND METHODS: This was a prospective cohort study nested in a clinical trial of intermittent preventive treatment in pregnancy for malaria with either dihydroartemisinin-piperaquine with/without azithromycin or sulfadoxine-pyrimethamine in Korogwe District, north-eastern Tanzania (Clinicaltrials.gov: NCT03208179). Newborns were weighed at birth or in the immediate hours after birth and then daily for 1 week. Reference charts, nadir, time to regain weight, and prediction maps were generated using nonlinear mixed-effects models fitted to the longitudinal data, incorporating interindividual variation as random effects. Predictions and prediction standard deviations were computed using a linear approximation approach. RESULTS: Between March and December 2019, 513 live newborns with birthweights measured within 24 h of delivery were weighed daily for 1 week. Complete datasets were available from 476 exclusively breastfed newborns. There was a rapid decline in weight shortly after delivery. The average weight loss, time of nadir, and time to regain weight were 4.3% (95% confidence interval [CI] 3.8-4.9) at 27 h (95% CI 24-30) and 105 h (95% CI 91-120) in boys and 4.9% (95% CI 4.2-5.6) at 28 h (95% CI 23-33) and 114 h (95% CI 93-136) in girls, respectively. The data were used to generate prediction maps with 1-h time intervals and 0.05 kg weight increments showing the predicted birthweights and weight-for-age and weight-change-for-age reference charts depicting variation in weight loss from <1 to >10%. CONCLUSIONS: The prediction maps and reference charts can be used by researchers in low-resource settings to retrospectively estimate birthweights using weights collected up to 168 h after delivery, thereby maximizing data utilization. Clinical practitioners can also use the prediction maps to retrospectively classify newborns as low birthweight or small for gestational age.
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Aleitamento Materno , Retardo do Crescimento Fetal , Peso ao Nascer , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Estudos Retrospectivos , Redução de PesoRESUMO
Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp with SP, we monitored birth outcomes in women followed up from before conception or from the first trimester until delivery. Women infected with sextuple haplotypes, in the early second trimester specifically, delivered newborns with a lower birth weight compared with women who did not have malaria during pregnancy (difference, -267 g; 95% confidence interval, -454 to -59; Pâ =â .01) and women infected with less SP-resistant haplotypes (-461 g; -877 to -44; Pâ =â .03). Thus, sextuple haplotype infections seem to affect the effectiveness of SP for IPTp and directly affect birth outcome by lowering birth weight. Close monitoring and targeted malaria control during early pregnancy is therefore crucial to improving birth outcomes.
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Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Sulfadoxina/uso terapêutico , Adulto , Antimaláricos/farmacologia , Peso ao Nascer , Combinação de Medicamentos , Resistência a Medicamentos/efeitos dos fármacos , Resistência a Medicamentos/genética , Feminino , Humanos , Recém-Nascido , Masculino , Plasmodium falciparum/genética , Gravidez , Complicações Parasitárias na Gravidez/diagnóstico , Complicações Parasitárias na Gravidez/tratamento farmacológico , Resultado da Gravidez , Segundo Trimestre da Gravidez , Pirimetamina/uso terapêuticoRESUMO
BACKGROUND: Cryptosporidiosis has been identified as one of the major causes of diarrhea and diarrhea-associated deaths in young children in sub-Saharan Africa. This study traces back Cryptosporidium-positive children to their human and animal contacts to identify transmission networks. METHODS: Stool samples were collected from children < 5 years of age with diarrhea in Gabon, Ghana, Madagascar, and Tanzania. Cryptosporidium-positive and -negative initial cases (ICs) were followed to the community, where stool samples from households, neighbors, and animal contacts were obtained. Samples were screened for Cryptosporidium species by immunochromatographic tests and by sequencing the 18S ribosomal RNA gene and further subtyped at the 60 kDa glycoprotein gene (gp60). Transmission clusters were identified and risk ratios (RRs) calculated. RESULTS: Among 1363 pediatric ICs, 184 (13%) were diagnosed with Cryptosporidium species. One hundred eight contact networks were sampled from Cryptosporidium-positive and 68 from negative ICs. Identical gp60 subtypes were detected among 2 or more contacts in 39 (36%) of the networks from positive ICs and in 1 contact (1%) from negative ICs. In comparison to Cryptosporidium-negative ICs, positive ICs had an increased risk of having Cryptosporidium-positive household members (RR, 3.6 [95% confidence interval {CI}, 1.7-7.5]) or positive neighboring children (RR, 2.9 [95% CI, 1.6-5.1]), but no increased risk of having positive animals (RR, 1.2 [95% CI, .8-1.9]) in their contact network. CONCLUSIONS: Cryptosporidiosis in rural sub-Saharan Africa is characterized by infection clusters among human contacts, to which zoonotic transmission appears to contribute only marginally.
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Criptosporidiose , Cryptosporidium , Animais , Criança , Pré-Escolar , Criptosporidiose/epidemiologia , Cryptosporidium/genética , Fezes , Gabão , Genótipo , Gana , Humanos , Madagáscar , TanzâniaRESUMO
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.
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Anemia/epidemiologia , Malária Falciparum/epidemiologia , Parasitemia/epidemiologia , Plasmodium falciparum/isolamento & purificação , Adolescente , Anemia/parasitologia , Infecções Assintomáticas/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Malária Falciparum/parasitologia , Masculino , Parasitemia/parasitologia , Tanzânia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Pregnancy malaria has a negative impact on fetal outcome. It is uncertain whether infections in early pregnancy have a clinical impact by impeding the development of the placental vasculature. METHODS: Tanzanian women (n = 138) were closely monitored during pregnancy. Placentas collected at birth were investigated using stereology to establish the characteristics of placental villi and vessels. Placental vasculature measures were compared between women infected with malaria and controls. RESULTS: Compared with controls, placentas from women infected with malaria before a gestational age (GA) of 15 weeks had a decreased volume of transport villi (mean decrease [standard deviation], 12.45 [5.39] cm3; P = .02), an increased diffusion distance in diffusion vessels (mean increase, 3.33 [1.27] µm; P = .01), and a compensatory increase in diffusion vessel surface area (mean increase, 1.81 [0.74 m2]; P = .02). In women who had malaria before a GA of 15 weeks diffusion vessel surface area and transport vessel length distance were positive predictors for birth weight (multilinear regression: P = .007 and P = .055 for diffusion surface area and transport length, respectively) and GA at delivery (P = .005 and P = .04). CONCLUSIONS: Malaria infection in early pregnancy impedes placental vascular development. The resulting phenotypic changes, which can be detected at delivery, are associated with birth weight and gestational length. CLINICAL TRIALS REGISTRATION: NCT02191683.
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Vasos Sanguíneos/crescimento & desenvolvimento , Vasos Sanguíneos/patologia , Malária/patologia , Placenta/patologia , Placentação , Complicações Infecciosas na Gravidez/patologia , Adolescente , Adulto , Feminino , Humanos , Recém-Nascido , Estudos Longitudinais , Gravidez , Resultado da Gravidez , Tanzânia , Adulto JovemRESUMO
BACKGROUND: Salmonella enterica including Salmonella Typhi and nontyphoidal Salmonella (NTS) are the predominant cause of community-acquired bloodstream infections in sub-Saharan Africa (sSA). Multiple-drug resistance and emerging fluoroquinolone resistance are of concern. Data on the age distribution of typhoid fever in sSA are scarce but essential for typhoid conjugate vaccine policy. We sought to describe Salmonella bloodstream infections, antimicrobial resistance, and age distribution at a rural district hospital in northeastern Tanzania. METHODS: From 2008 to 2016, febrile children or children with a history of fever aged 1 month to 5 years admitted to Korogwe District Hospital were enrolled. Demographic, clinical data and blood cultures were collected. Organisms were identified by conventional microbiological methods, and antimicrobial susceptibility test was done by disc diffusion. RESULTS: Of 4176 participants receiving blood cultures, 383 (9.2 %) yielded pathogens. Of pathogens, 171 (44.6%) were Salmonella enterica of which 129 (75.4%) were Salmonella Typhi, and 42 (24.6%) were NTS. The median (interquartile range age of participants was 13.1 (6.3-28.0) months for those with Salmonella Typhi and 11.5 (8.5-23.4) months for NTS. Of 129 Salmonella Typhi, 89 (89.9%) were resistant to amoxicillin, 85 (81.0%) to chloramphenicol, and 93 (92.1%) to trimethoprim-sulfamethoxazole compared with 22 (62.9%), 15 (39.4%), and 27 (79.4%), respectively, for NTS. Multidrug resistance was present in 68 (81.0%) of Salmonella Typhi and 12 (41.4%) of NTS. CONCLUSION: Salmonella Typhi was the leading cause of bloodstream infection among infants and young children <2 years of age admitted to Korogwe District Hospital. Multidrug resistance was common, highlighting a role for typhoid conjugate vaccine into routine infant vaccine schedules.
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Antibacterianos/farmacologia , Febre/microbiologia , Infecções por Salmonella/sangue , Infecções por Salmonella/epidemiologia , Salmonella enterica/efeitos dos fármacos , Hemocultura , Pré-Escolar , Infecções Comunitárias Adquiridas/sangue , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Feminino , Febre/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , População Rural , Tanzânia/epidemiologiaRESUMO
Cerebral malaria (CM) is a potentially deadly outcome of Plasmodium falciparum malaria that is precipitated by sequestration of infected erythrocytes (IEs) in the brain. The adhesion of IEs to brain endothelial cells is mediated by a subtype of parasite-encoded erythrocyte membrane protein 1 (PfEMP1) that facilitates dual binding to host intercellular adhesion molecule 1 (ICAM-1) and endothelial protein receptor C (EPCR). The PfEMP1 subtype is characterized by the presence of a particular motif (DBLß_motif) in the constituent ICAM-1-binding DBLß domain. The rate of natural acquisition of DBLß_motif-specific IgG antibodies and the ability to induce such antibodies by vaccination are unknown, and the aim of this study was to provide such data. We used an enzyme-linked immunosorbent assay (ELISA) to measure DBLß-specific IgG in plasma from Ghanaian children with malaria. The ability of human immune plasma and DBLß-specific rat antisera to inhibit the interaction between ICAM-1 and DBLß was assessed using ELISA and in vitro assays of IE adhesion under flow. The acquisition of DBLß_motif-specific IgG coincided with age-specific susceptibility to CM. Broadly cross-reactive antibodies inhibiting the interaction between ICAM-1 and DBLß_motif domains were detectable in immune plasma and in sera of rats immunized with specific DBLß_motif antigens. Importantly, antibodies against the DBLß_motif inhibited ICAM-1-specific in vitro adhesion of erythrocytes infected by four of five P. falciparum isolates from cerebral malaria patients. We conclude that natural exposure to P. falciparum as well as immunization with specific DBLß_motif antigens can induce cross-reactive antibodies that inhibit the interaction between ICAM-1 and a broad range of DBLß_motif domains. These findings raise hope that a vaccine designed specifically to prevent CM is feasible.
Assuntos
Imunoglobulina G/imunologia , Molécula 1 de Adesão Intercelular/metabolismo , Malária Cerebral/imunologia , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/metabolismo , Adolescente , Motivos de Aminoácidos , Anticorpos Neutralizantes/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Sítios de Ligação , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Gana , Humanos , Imunoglobulina G/metabolismo , Lactente , Vacinas Antimaláricas/imunologia , Malária Cerebral/metabolismo , Malária Cerebral/parasitologia , Malária Falciparum/metabolismo , Malária Falciparum/parasitologia , Ligação Proteica/imunologia , Domínios e Motivos de Interação entre Proteínas , Proteínas de Protozoários/química , TanzâniaRESUMO
OBJECTIVES: To determine risk factors of pre-hypertension and hypertension in a cohort of 1247 rural Tanzanian women before conception. METHODS: Demographic and socioeconomic data, anthropometric measurements, past medical and obstetric history and other risk factors for pre-hypertension and hypertension were collected using a structured questionnaire. Multiple logistic regression analysis was used to evaluate the associations between anthropometric indices and other risk factors of pre-hypertension and hypertension. The predictive power of different anthropometric indicators for identification of pre-hypertension and hypertension patients was determined by Receiver Operating Characteristic curves (ROC). RESULTS: The median (range) age was 28.0 (18-40) years. The age-standardised prevalences of pre-hypertension and hypertension were 37.2 (95% CI 34.0-40.6) and 8.5% (95%CI 6.7-10.8), respectively. Of hypertensive patients (n = 98), only 20 (20.4%) were aware of their condition. In multivariate analysis, increasing age, obesity and haemoglobin levels were significantly associated with pre-hypertension and hypertension. CONCLUSION: Despite a low prevalence of hypertension, over one third of the women had pre-hypertension. This poses a great challenge ahead as pre-hypertensive women may progress into hypertension as they grow older without appropriate interventions. Obesity was the single most important modifiable risk factor for pre-hypertension and hypertension.
Assuntos
Hipertensão/epidemiologia , Pré-Hipertensão/epidemiologia , População Rural/estatística & dados numéricos , Adolescente , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Prevalência , Fatores de Risco , Tanzânia , Adulto JovemRESUMO
BACKGROUND: Four studies previously indicated that the effect of malaria infection during pregnancy on the risk of low birthweight (LBW; <2,500 g) may depend upon maternal nutritional status. We investigated this dependence further using a large, diverse study population. METHODS AND FINDINGS: We evaluated the interaction between maternal malaria infection and maternal anthropometric status on the risk of LBW using pooled data from 14,633 pregnancies from 13 studies (6 cohort studies and 7 randomized controlled trials) conducted in Africa and the Western Pacific from 1996-2015. Studies were identified by the Maternal Malaria and Malnutrition (M3) initiative using a convenience sampling approach and were eligible for pooling given adequate ethical approval and availability of essential variables. Study-specific adjusted effect estimates were calculated using inverse probability of treatment-weighted linear and log-binomial regression models and pooled using a random-effects model. The adjusted risk of delivering a baby with LBW was 8.8% among women with malaria infection at antenatal enrollment compared to 7.7% among uninfected women (adjusted risk ratio [aRR] 1.14 [95% confidence interval (CI): 0.91, 1.42]; N = 13,613), 10.5% among women with malaria infection at delivery compared to 7.9% among uninfected women (aRR 1.32 [95% CI: 1.08, 1.62]; N = 11,826), and 15.3% among women with low mid-upper arm circumference (MUAC <23 cm) at enrollment compared to 9.5% among women with MUAC ≥ 23 cm (aRR 1.60 [95% CI: 1.36, 1.87]; N = 9,008). The risk of delivering a baby with LBW was 17.8% among women with both malaria infection and low MUAC at enrollment compared to 8.4% among uninfected women with MUAC ≥ 23 cm (joint aRR 2.13 [95% CI: 1.21, 3.73]; N = 8,152). There was no evidence of synergism (i.e., excess risk due to interaction) between malaria infection and MUAC on the multiplicative (p = 0.5) or additive scale (p = 0.9). Results were similar using body mass index (BMI) as an anthropometric indicator of nutritional status. Meta-regression results indicated that there may be multiplicative interaction between malaria infection at enrollment and low MUAC within studies conducted in Africa; however, this finding was not consistent on the additive scale, when accounting for multiple comparisons, or when using other definitions of malaria and malnutrition. The major limitations of the study included availability of only 2 cross-sectional measurements of malaria and the limited availability of ultrasound-based pregnancy dating to assess impacts on preterm birth and fetal growth in all studies. CONCLUSIONS: Pregnant women with malnutrition and malaria infection are at increased risk of LBW compared to women with only 1 risk factor or none, but malaria and malnutrition do not act synergistically.
Assuntos
Recém-Nascido de Baixo Peso/fisiologia , Malária/epidemiologia , Desnutrição/epidemiologia , África Subsaariana/epidemiologia , Ásia/epidemiologia , Feminino , Humanos , Recém-Nascido , Malária/parasitologia , Desnutrição/etiologia , Ilhas do Pacífico/epidemiologia , Gravidez , PrevalênciaRESUMO
BACKGROUND: Endothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria. This study determined the frequencies of PROCR haplotypes H1-4 and plasma levels of sEPCR in a Tanzanian study population to investigate a possible association with severe malaria. METHODS: Study participants were children under 5 years of age admitted at the Korogwe District Hospital (N = 143), and diagnosed as having severe malaria (N = 52; including cerebral malaria N = 17), uncomplicated malaria (N = 24), or an infection other than malaria (N = 67). In addition, blood samples from 71 children living in nearby villages were included. The SNPs defining the haplotypes of PROCR gene were determined by post-PCR ligation detection reaction-fluorescent microsphere assay. RESULTS: Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001). No difference in the frequency of H3 was found between the non-malaria patients, malaria patients or the village population (P > 0.1). Plasma levels of sEPCR differed between these three groups, with higher sEPCR levels in the village population compared to the hospitalized patients (P < 0.001) and higher levels in malaria patients compared to non-malaria patients (P = 0.001). However, no differences were found in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria. CONCLUSION: Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming earlier findings, however, in this Tanzanian population; neither PROCR haplotype nor level of sEPCR was associated with severe malaria, however, larger studies are needed to confirm these findings.
Assuntos
Antígenos CD/sangue , Antígenos CD/genética , Resistência à Doença , Haplótipos , Malária Falciparum/genética , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/genética , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Receptor de Proteína C Endotelial , Feminino , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único , TanzâniaRESUMO
Diarrheal diseases are important causes of morbidity and mortality, worldwide. The occurrence of multiple pathogens in stool samples of symptomatic and asymptomatic individuals in resource-limited countries have been repeatedly described. In this study, we assessed the differentiated effects of combined pathogen detections on recorded symptoms. A case-control study was conducted among 620 under-five-year-old children in rural northeastern Tanzania with emphasis of multiple detection. The median age of children was 11 months (IQR = 7, 20), and 52.1% were male. Cases (50.2%, n = 157) were less likely than controls (64.5%, n = 198) to have multiple colonization with gastrointestinal tract (GIT) pathogens. The children's age was positively associated with the likelihood of harboring multiple GIT pathogens [OR, 1.02, 95% CI = 1.01, 1.04]. Shigella spp./enteroinvasive Escherichia coli (EIEC) [OR = 2.80, 95% CI 1.62, 4.83] and norovirus [OR = 2.04, 95% CI 1.23, 3.39] were more common in cases and were strongly associated with diarrhea, while enteroaggregative E. coli (EAEC) [OR = 0.23, 95%CI 0.17-0.33] were more common in controls. Diarrheal diseases in under-five children from rural Tanzania are likely to be due to infections with Shigella spp./EIEC, and norovirus with strongly age-dependent associations.
Assuntos
Diarreia , População Rural , Humanos , Tanzânia/epidemiologia , Masculino , Feminino , Estudos de Casos e Controles , Diarreia/epidemiologia , Diarreia/microbiologia , Lactente , Pré-Escolar , População Rural/estatística & dados numéricos , Shigella/isolamento & purificação , Fezes/microbiologia , Trato Gastrointestinal/microbiologia , Norovirus/isolamento & purificação , Escherichia coli/isolamento & purificaçãoRESUMO
OBJECTIVE: Intermittent Preventive Treatment of schoolchildren (IPTsc) is recommended by WHO as a strategy to protect against malaria; to explore whether IPTsc with dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) cause a selection of molecular markers in Plasmodium falciparum genes associated with resistance in children in seven schools in Tanga region, Tanzania. METHODS: SNPs in P. falciparum genes Pfmdr1, Pfexo, Pfkelch13, and Pfcrt and copy number variations in Pfplasmepsin-2 and Pfmdr1 were assessed in samples collected at 12 months (visit 4, n=74) and 20 months (visit 6, n=364) after initiation of IPTsc and compared with the baseline prevalence (n=379). RESULTS: The prevalence of Pfmdr1 N86 and Pfexo 415G was >99% and 0%, respectively without any temporal differences observed. The prevalence of Pfmdr1 184F changed significantly from baseline (52.2%) to visit 6 (64.6%) (χ2=6.11, P=0.013), but no differences were observed between the treatment arms (χ2=0.05, P=0.98). Finally, only minor differences in the amplification of Pfmdr1 were observed; from 10.2% at baseline to 16.7% at visit 6 (χ2=0.98, P=0.32). CONCLUSIONS: The IPTsc strategy does not seem to pose a risk for the selection of markers associated with DP or ASAQ resistance. Continuously and timely surveillance of markers of antimalarial drug resistance is recommended.
Assuntos
Amodiaquina , Antimaláricos , Artemisininas , Combinação de Medicamentos , Resistência a Medicamentos , Malária Falciparum , Plasmodium falciparum , Humanos , Antimaláricos/uso terapêutico , Antimaláricos/farmacologia , Tanzânia/epidemiologia , Criança , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Falciparum/parasitologia , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Resistência a Medicamentos/genética , Masculino , Feminino , Amodiaquina/uso terapêutico , Artemisininas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Quinolinas/uso terapêutico , Pré-Escolar , Proteínas de Protozoários/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Marcadores Genéticos , Variações do Número de Cópias de DNA , PiperazinasRESUMO
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.