Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization.

The combination antimalarial therapy of artemisinin-naphthoquine (ART-NQ) was developed as a single-dose therapy, aiming to improve adherence relative to the multiday schedules of other artemisinin combination therapies. The pharmacokinetics of ART-NQ has not been well characterized, especially in children. A pharmacokinetic study was conducted in adults and children over 5 years of age (6 to 10, 11 to 17, and ≥18 years of age) with uncomplicated malaria in Tanzania. The median weights for the three age groups were 20, 37.5, and 55 kg, respectively. Twenty-nine patients received single doses of 20 mg/kg of body weight for artemisinin and 8 mg/kg for naphthoquine, and plasma drug concentrations were assessed at 13 time points over 42 days from treatment. We used nonlinear mixed-effects modeling to interpret the data, and allometric scaling was employed to adjust for the effect of body size. The pharmacokinetics of artemisinin was best described by one-compartment model and that of naphthoquine by a two-compartment disposition model. Clearance values for a typical patient (55-kg body weight and 44.3-kg fat-free mass) were estimated as 66.7 L/h (95% confidence interval [CI], 57.3 to 78.5 L/h) for artemisinin and 44.2 L/h (95% CI, 37.9 to 50.6 L/h) for naphthoquine. Nevertheless, we show via simulation that patients weighing ≥70 kg achieve on average a 30% lower day 7 concentration compared to a 48-kg reference patient at the doses tested, suggesting dose increases may be warranted to ensure adequate exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT01930331.).

HIV Infection Functionally Impairs Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses.

Human immunodeficiency virus (HIV) infection is the major risk factor predisposing for Mycobacterium tuberculosis progression from latent tuberculosis infection (LTBI) to tuberculosis disease (TB). Since long-term-treated aviremic HIV-infected individuals remained at higher risk of developing TB than HIV-uninfected individuals, we hypothesized that progression from LTBI to pulmonary TB (PTB) might be due not only to CD4 T-cell depletion but also to M. tuberculosis-specific CD4 T-cell functional impairment. To test this hypothesis, M. tuberculosis-specific T-cell frequencies and cytokine profiles were investigated in untreated Tanzanian individuals suffering from LTBI (n = 20) or PTB (n = 67) and compared to those of untreated M. tuberculosis/HIV-coinfected individuals suffering from LTBI (n = 15) or PTB (n = 10). We showed that HIV infection significantly reduced the proportion of Th2 (interleukin 4 [IL-4]/IL-5/IL-13) producing M. tuberculosis-specific CD4 T cells and IL-2-producing M. tuberculosis-specific CD4 and CD8 T cells in individuals with LTBI or PTB (P < 0.05). Interestingly, the loss of IL-2 production was associated with a significant increase of PD-1 expression on M. tuberculosis-specific CD4 and CD8 T cells (P < 0.05), while the loss of Th2 cytokine production was associated with a significant reduction of Gata-3 expression in memory CD4 T cells (P < 0.05). Finally, we showed that the serum levels of IL-1α, IL-6, C-reactive protein (CRP), IL-23, and IP-10 were significantly reduced in M. tuberculosis/HIV-coinfected individuals with PTB compared to those in HIV-negative individuals with PTB (P < 0.05), suggesting that HIV infection significantly suppresses M. tuberculosis-induced systemic proinflammatory cytokine responses. Taken together, this study suggests that in addition to depleting M. tuberculosis-specific CD4 T cells, HIV infection significantly impairs functionally favorable M. tuberculosis-specific CD4 T-cell responses in Tanzanian individuals with LTBI or PTB.IMPORTANCEMycobacterium tuberculosis and human immunodeficiency virus (HIV) infections are coendemic in several regions of the world, and M. tuberculosis/HIV-coinfected individuals are more susceptible to progression to tuberculosis disease. We therefore hypothesized that HIV infection would potentially impair M. tuberculosis-specific protective immunity in individuals suffering from latent tuberculosis infection (LTBI) or active pulmonary tuberculosis (PTB). In this study, we demonstrated that M. tuberculosis/HIV-coinfected individuals have fewer circulating M. tuberculosis-specific CD4 T cells and that those that remained were functionally impaired in both LTBI and PTB settings. In addition, we showed that HIV infection significantly interferes with M. tuberculosis-induced systemic proinflammatory cytokine/chemokine responses. Taken together, these data suggest that HIV infection impairs functionally favorable M. tuberculosis-specific immunity.

Enterobiasis and strongyloidiasis and associated co-infections and morbidity markers in infants, preschool- and school-aged children from rural coastal Tanzania: a cross-sectional study.

BACKGROUND: There is a paucity of data pertaining to the epidemiology and public health impact of Enterobius vermicularis and Strongyloides stercoralis infections. We aimed to determine the extent of enterobiasis, strongyloidiasis, and other helminth infections and their association with asymptomatic Plasmodium parasitaemia, anaemia, nutritional status, and blood cell counts in infants, preschool-aged (PSAC), and school-aged children (SAC) from rural coastal Tanzania. METHODS: A total of 1,033 children were included in a cross-sectional study implemented in the Bagamoyo district in 2011/2012. Faecal samples were examined for intestinal helminth infections using a broad set of quality controlled methods. Finger-prick blood samples were subjected to filariasis and Plasmodium parasitaemia testing and full blood cell count examination. Weight, length/height, and/or mid-upper arm circumference were measured and the nutritional status determined in accordance with age. RESULTS: E. vermicularis infections were found in 4.2% of infants, 16.7%, of PSAC, and 26.3% of SAC. S. stercoralis infections were detected in 5.8%, 7.5%, and 7.1% of infants, PSAC, and SAC, respectively. Multivariable regression analyses revealed higher odds of enterobiasis in children of all age-groups with a reported anthelminthic treatment history over the past six months (odds ratio (OR): 2.15; 95% confidence interval (CI): 1.22 - 3.79) and in SAC with a higher temperature (OR: 2.21; CI: 1.13 - 4.33). Strongyloidiasis was associated with eosinophilia (OR: 2.04; CI: 1.20-3.48) and with Trichuris trichiura infections (OR: 4.13; CI: 1.04-16.52) in children of all age-groups, and with asymptomatic Plasmodium parasitaemia (OR: 13.03; CI: 1.34 - 127.23) in infants. None of the investigated helminthiases impacted significantly on the nutritional status and anaemia, but moderate asymptomatic Plasmodium parasitaemia was a strong predictor for anaemia in children aged older than two years (OR: 2.69; 95% CI: 1.23 - 5.86). CONCLUSIONS: E. vermicularis and S. stercoralis infections were moderately prevalent in children from rural coastal Tanzania. Our data can contribute to inform yet missing global burden of disease and prevalence estimates for strongyloidiasis and enterobiasis. The association between S stercoralis and asymptomatic Plasmodium parasitaemia found here warrants further comprehensive investigations.

RAIN: machine learning-based identification for HIV-1 bNAbs.

Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoires is still lacking. Here, we develop a straightforward computational method for the Rapid Automatic Identification of bNAbs (RAIN) based on machine learning methods. In contrast to other approaches, which use one-hot encoding amino acid sequences or structural alignment for prediction, RAIN uses a combination of selected sequence-based features for the accurate prediction of HIV-1 bNAbs. We demonstrate the performance of our approach on non-biased, experimentally obtained and sequenced BCR repertoires from HIV-1 immune donors. RAIN processing leads to the successful identification of distinct HIV-1 bNAbs targeting the CD4-binding site of the envelope glycoprotein. In addition, we validate the identified bNAbs using an in vitro neutralization assay and we solve the structure of one of them in complex with the soluble native-like heterotrimeric envelope glycoprotein by single-particle cryo-electron microscopy (cryo-EM). Overall, we propose a method to facilitate and accelerate HIV-1 bNAbs discovery from non-selected immune repertoires.

The effects of prenatal and postnatal high-dose vitamin B-12 supplementation on human milk vitamin B-12: a randomized, double-blind, placebo-controlled trial in Tanzania.

BACKGROUND: Vitamin B-12 status in human milk (HM) has critical implications for infant growth and development. Few studies have separately evaluated the effects of prenatal and postnatal maternal high-dose vitamin B-12 supplementation on HM vitamin B-12 concentration. OBJECTIVES: This randomized controlled trial aimed to assess the effects of prenatal and postnatal vitamin B-12 supplementation on HM vitamin B-12 at 6 wk and 7 mo postpartum. METHODS: Pregnant women were enrolled in Dar es Salaam, Tanzania, between 2001 and 2004. From recruitment (12-27 weeks of gestation) through 6 wk postpartum, participants were randomly assigned to daily oral multiple micronutrient supplementation or placebo. From 6 wk to 18 mo postpartum, a subset of participants was randomly assigned to a postnatal supplement or placebo. The supplement included 50 µg/d of vitamin B-12 and various other vitamins. HM vitamin B-12 concentrations were analyzed at 6 wk and 7 mo postpartum for 412 participants. RESULTS: The prevalence of HM vitamin B-12 of <310 pmol/L was 73.3% and 68.4% at 6 wk and 7 mo postpartum, respectively. Prenatal supplementation increased HM vitamin B-12 concentration (percent difference: 34.4; 95% CI: 17.0, 54.5; P < 0.001) at 6 wk; this effect was not present at 7 mo. Postnatal supplementation increased HM vitamin B-12 concentration (percent difference: 15.9; 95% CI: 1.91, 31.9; P = 0.025) at 7 mo. Effect modification between prenatal and postnatal supplementation on HM vitamin B-12 status at 7 mo was found, with the effects of prenatal and postnatal supplements more pronounced among those receiving control during the other period; the prenatal supplement had a greater effect with postnatal control, and the postnatal supplement had a greater effect with prenatal control. CONCLUSIONS: Prenatal maternal vitamin B-12 supplementation has benefits on short-term HM status, and postnatal maternal vitamin B-12 supplementation has benefits on long-term HM status. This trial was registered at clinicaltrials.gov as NCT00197548. https://clinicaltrials.gov/ct2/show/NCT00197548.

Solicited Cough Sound Analysis for Tuberculosis Triage Testing: The CODA TB DREAM Challenge Dataset.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

Pilot deployment of a community health care worker in distributing and offering the COVID-19 AgRDT in Tanzania.

A pilot implementation of the rapid diagnostic test program was performed to collect evidence of the feasibility, acceptability, and uptake of the COVID-19 AgRDT in Tanzania. We conducted a prospective cross-sectional study in the community to provide quantitative details of the pilot implementation of the antigen rapid diagnostic test (AgRDT) in Tanzania. This study was undertaken between March 2022 and September 2022. The pilot was implemented by distributing and offering test kits to people suspected of having COVID-19 in Dar es Salaam through community health workers. A total of 1039 participants consented to participate in the survey. All the participants reported having heard about the disease. The radio was the main source (93.2%) of information on COVID-19. With regard to prevention measures, approximately 930 (89.5%) of the respondents thought that COVID-19 could be prevented. Approximately 1035 (99.6%) participants reported that they were willing to have a COVID-19 AgRDT test and wait for 20 min for the results. With regard to the participants' opinions on the AgRDT device, the majority 907 (87.3%) felt comfortable with the test, and 1,029 (99.0%) were very likely to recommend the AgRDT test to their friends. The majority of participants 848 (83.1%) mentioned that they would be willing to pay for the test if it was not available for free. The results suggest overall good acceptance of the COVID-19 AgRDT test. It is evident that the use of trained community healthcare workers allows easy screening of all possible suspects and helps them receive early treatment.

Understanding Sociodemographic Factors and Reasons Associated with COVID-19 Vaccination Hesitance among Adults in Tanzania: A Mixed-Method Approach.

Although studies on COVID-19 vaccine hesitancy are being undertaken widely worldwide, there is limited evidence in Tanzania. This study aims to assess the sociodemographic factors associated with COVID-19 vaccine hesitancy and the reasons given by unvaccinated study participants. We conducted a mixed-method cross-sectional study with two components-health facilities and communities-between March and September 2022. A structured questionnaire and in-depth interviews were used to collect quantitative and qualitative data, respectively. A total of 1,508 individuals agreed to participate in the survey and explained why they had not vaccinated against COVID-19. Of these participants, 62% indicated they would accept the vaccine, whereas 38% expressed skepticism. In a multivariate regression analysis, adult study participants 40 years and older were significantly more likely to report not intending to be vaccinated (adjusted odds ratio [AOR], 1.28; 95% CI, 1.01-1.61; P = 0.04) than youth and middle-aged study participants between 18 and 40 years. Furthermore, female study participants had a greater likelihood of not intending to be vaccinated (AOR, 1.51; 95% CI, 1.19-1.90; P = 0.001) than male study participants. The study identified fear of safety and short-term side effects, and lack of trust of the COVID-19 vaccine; belief in spiritual or religious views; and belief in local remedies and other precautions or preventive measures as the major contributors to COVID-19 vaccine hesitancy in Tanzania. Further empirical studies are needed to confirm these findings and to understand more fully the reasons for vaccine hesitancy in different demographic groups.

The High Burden and Predictors of Anemia Among Infants Aged 6 to 12 Months in Dar es Salaam, Tanzania.

BACKGROUND: Despite several interventions, the prevalence of anemia and related complications remains high among infants in Tanzania. OBJECTIVE: We sought to determine the predictors of iron-deficiency anemia (IDA) among infants of HIV-negative women in Dar es Salaam, Tanzania. METHODS: Cross-sectional analysis of 2826 mother-infant pairs who participated in a trial of vitamins and perinatal outcomes in Dar es Salaam, Tanzania. Hemoglobin and mean corpuscular volume were used to determine the prevalence of anemia among infants at 6 and 12 months. Multiple logistic regression was used to determine the maternal and infant risk factors for anemia during infancy. RESULTS: We found high prevalence of anemia (90%) and IDA (44.2%) among infants. Higher maternal education (odds ratio [OR] = 0.52), maternal normal hemoglobin at enrollment (OR = 0.68) and during the early postpartum period reduced the odds of IDA at 6 months (OR = 0.56). The odds of IDA at 6 months were higher among males (OR = 1.65), wealth score below median (OR = 1.35), low birth weight (LBW; OR = 1.75), and small for gestational age (SGA) infants below the third centile (OR = 1.95) or third to less than fifth centile (OR = 2.29). Higher maternal education lowered the odds of IDA at 12 months (OR = 0.25). Wealth score below median (OR = 1.44), preterm delivery (OR = 1.94), SGA (less than third centile; OR = 2.40), and LBW (OR = 2.89) increased the odds of IDA during infancy in the study population. Dietary diversity was low for infants and women in the study sample. CONCLUSION: Interventions to reduce the risk of infant IDA should address women's education, improvement of wealth status, and optimal care for premature, SGA, and LBW infants.

Motivations and barriers for healthy participants to participate in herbal remedy clinical trial in Tanzania: A qualitative study based on the theory of planned behaviour.

BACKGROUND: The success of any randomized clinical trial relies on the willingness of people to be recruited in the trial. However, 90% of all clinical trials worldwide have been reported to have failed to recruit the required number of trial participants within the scheduled time. This study aimed to qualitatively explore the motivations and barriers for healthy participants to participate in herbal remedy clinical trials in Tanzania. MATERIALS AND METHODS: This study used a qualitative descriptive research design based on the theory of planned behaviour. A total of five Focus Group Discussions (FGD) were conducted at Bagamoyo Clinical Trial Facility from 29 to 30 May 2021. Each group consisted of 5 to 10 participants. The participants of the study were 30 healthy males aged 18 to 45 male who participated in the clinical trial that evaluated the safety, tolerability, and efficacy of Maytenus Senegalensis. The focus group discussions were recorded audio-recorded. Verbatim transcription and thematic analysis were performed on the data. RESULTS: The prominent motivations mentioned were the opportunity for self-development, altruism, flexible study visit schedule, and financial compensation. Furthermore, the Participants' mothers and friends were reported as those most likely to approve of participation in an herbal remedy. The most mentioned barriers were inconvenience related to time commitment requirements, possible side effects, inflexible study visit schedule, and having other commitments. Moreover, the participants' father was reported to be more likely to disapprove of participation in a clinical trial of herbal remedy clinical trial. CONCLUSIONS: The results of this study showed that the motivations and barriers of healthy participants to participate in clinical trials of herbal remedies are varied and that participants are motivated by more than financial gains. The identified motivations and barriers can be used as a guideline to improve the design of recruitment and retention strategies for herbal remedy clinical trials.

Safety and Tolerability of an Antimalarial Herbal Remedy in Healthy Volunteers: An Open-Label, Single-Arm, Dose-Escalation Study on Maytenus senegalensis in Tanzania.

BACKGROUND: Though Maytenus senegalensis is one of the medicinal plants widely used in traditional medicine to treat infectious and inflammatory diseases in Africa, there is a lack of safety data regarding its use. Therefore, the study aimed to asselss the safety and tolerability of the antimalarial herbal remedy M. senegalensis. MATERIAL AND METHODS: The study design was an open-label, single-arm, dose-escalation. Twelve eligible male healthy Tanzanians aged 18 to 45 years were enrolled in four study dose groups. Volunteers' safety and tolerability post-investigational-product administration were monitored on days 0 to 7,14, and 56. RESULTS: There were no deaths or serious adverse events in any of the study groups, nor any adverse events that resulted in premature discontinuation. The significant mean changes observed in WBC (p = 0.003), Neutrophils (p = 0.02), Lymphocytes (p = 0.001), Eosinophils (p = 0.009), Alanine aminotransferase (p = 0.002), Creatinine (p = 0.03) and Total bilirubin (p = 0.004) laboratory parameters were not associated with any signs of toxicity or clinical symptoms. CONCLUSIONS: M. senegalensis was demonstrated to be safe and tolerable when administered at a dose of 800 mg every eight hours a day for four days. This study design may be adapted to evaluate other herbal remedies.

Efficacy and safety of intravenous ferric carboxymaltose compared with oral iron for the treatment of iron deficiency anaemia in women after childbirth in Tanzania: a parallel-group, open-label, randomised controlled phase 3 trial.

BACKGROUND: Iron deficiency anaemia is of major concern in low-income settings, especially for women of childbearing age. Oral iron substitution efficacy is limited by poor compliance and iron depletion severity. We aimed to assess the efficacy and safety of intravenous ferric carboxymaltose versus oral iron substitution following childbirth in women with iron deficiency anaemia in Tanzania. METHODS: This parallel-group, open-label, randomised controlled phase 3 trial was done at Bagamoyo District Hospital and Mwananyamala Hospital, Tanzania. Eligible participants were close to delivery and had iron deficiency anaemia defined as a haemoglobin concentration of less than 110 g/L and a ferritin concentration of less than 50 µg/L measured within 14 days before childbirth. Participants were randomly assigned 1:1 to receive intravenous ferric carboxymaltose or oral iron, stratified by haemoglobin concentration and site. Intravenous ferric carboxymaltose was administered at a dose determined by the haemoglobin concentration and bodyweight (bodyweight 35 kg to <70 kg and haemoglobin ≥100 g/L: 1000 mg in one dose; bodyweight 35 kg to <70 kg and haemoglobin <100 g/L, or bodyweight ≥70 kg and haemoglobin ≥100 g/L: 1500 mg in two doses at least 7 days apart; bodyweight ≥70 kg and haemoglobin <100 g/L: 2000 mg in two doses at least 7 days apart). Oral iron treatment consisted of three dried ferrous sulphate tablets of 200 mg containing 60 mg of elementary iron and 5 mg of folic acid every morning. Oral treatment was to be taken for 3 months after haemoglobin normalisation. The primary outcome was haemoglobin normalisation (>115 g/L) at 6 weeks. Follow-up visits were at 6 weeks, and 3, 6, and 12 months. Analyses were done in the modified intention-to-treat population of participants who had a 6-week haemoglobin concentration result, using logistic and linear regression models for binary and continuous outcomes, adjusted for baseline haemoglobin concentration and site. This trial is registered with ClinicalTrials.gov, NCT02541708. FINDINGS: Between Oct 8, 2015, and March 14, 2017, 533 individuals were screened and 230 were enrolled and randomly assigned to a study group (114 to intravenous iron, 116 to oral iron). At 6 weeks, 94 (82%) participants in the intravenous iron group and 92 (79%) in the oral iron group were assessed for the primary outcome. 75 (80%) participants in the intravenous iron group and 47 (51%) in the oral iron group had normalised haemoglobin (odds ratio 4·65, 95% CI 2·33-9·27). There were two mild to moderate infusion-related adverse events; and five serious adverse events (three in the intravenous iron group, two in the oral iron group), unrelated to the study medication. INTERPRETATION: Intravenous iron substitution with ferric carboxymaltose was safe and yielded a better haemoglobin response than oral iron. To our knowledge, this is the first study to provide evidence of the benefits and safety of intravenous iron substitution in a low-income setting. FUNDING: Vifor Pharma, R Geigy-Stiftung, Freiwillige Akademische Gesellschaft, and Swiss Tropical and Public Health Institute.

Breast milk vitamin B12 concentration and incidence of diarrhea and respiratory infections among infants in urban Tanzania: a prospective cohort study.

OBJECTIVE: A recent trial of vitamin B12 supplementation among Indian children 6-30 months found no effect on the incidence of diarrhea and respiratory infections. These results differ with studies in adults that showed improvement of the immune response following treatment with vitamin B12. We sought to determine how the adequacy of vitamin B12 concentrations in breast milk could act as immune modulator and protect against the incidence of diarrhea and respiratory infections of children up to 18 months in urban Tanzania. RESULTS: A prospective cohort study was undertaken to determine the association of breast milk vitamin B12 concentration with the incidence of acute respiratory infection and diarrhea among infants in urban Tanzania. A random sample of 491 women enrolled in a trial of multivitamins provided milk for B12 analysis at or around 6 weeks postpartum. Of 491 women, 345 had breast milk vitamin B12 inadequacy (< 310 pmol/L). Using generalized estimating equations, we found no overall association of milk vitamin B12 concentration with incident diarrhea and acute respiratory infections in infants. Studies measuring longitudinal changes of breast milk B12 concentration over time are needed to clarify the role of breast milk vitamin B12 in childhood infections.

Vitamin B12 is Low in Milk of Early Postpartum Women in Urban Tanzania, and was not Significantly Increased by High dose Supplementation.

The effect of maternal multivitamin supplementation on breast milk vitamin B12 concentrations has not been examined in Tanzania, where the prevalence of maternal plasma B12 insufficiency is 25.6%. Multivitamins (containing 50 µg vitamin B12) or placebo were provided during pregnancy and in the postpartum period. Breast milk samples were collected at or around six weeks postpartum from 491 participants in a trial of multivitamins (NCT00197548). Linear and logistic regression models were used to examine the effect of supplements on vitamin B12 concentration in milk and its associations with other variables including potential confounders. Median vitamin B12 concentration in breast milk was 206 pmol/L and 70% of women had levels indicating inadequacy (<310 pmol/L). Multivitamin supplements did not significantly reduce the odds of inadequate vitamin B12 in breast milk, suggesting suboptimal absorption. A single unit increase in maternal hemoglobin at six weeks was associated with 18% lower odds of inadequate vitamin B12 in breast milk. Participants with higher BMI at baseline had double the odds of having inadequate vitamin B12 than the reference group (<22 kg/m2). Trials to determine the optimal dose, route, and duration of supplementation to improve maternal B12 status in Sub-Saharan Africa are of utmost importance.

Distribution and risk factors for Plasmodium and helminth co-infections: a cross-sectional survey among children in Bagamoyo district, coastal region of Tanzania.

BACKGROUND: Plasmodium and soil transmitted helminth infections (STH) are a major public health problem, particularly among children. There are conflicting findings on potential association between these two parasites. This study investigated the Plasmodium and helminth co-infections among children aged 2 months to 9 years living in Bagamoyo district, coastal region of Tanzania. METHODS: A community-based cross-sectional survey was conducted among 1033 children. Stool, urine and blood samples were examined using a broad set of quality controlled diagnostic methods for common STH (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, Enterobius vermicularis, Trichuris trichura), schistosoma species and Wuchereria bancrofti. Blood slides and malaria rapid diagnostic tests (mRDTs) were utilized for Plasmodium diagnosis. RESULTS: Out of 992 children analyzed, the prevalence of Plasmodium infection was 13% (130/992), helminth 28.5% (283/992); 5% (50/992) had co-infection with Plasmodium and helminth. The prevalence rate of Plasmodium, specific STH and co-infections increased significantly with age (p < 0.001), with older children mostly affected except for S. stercoralis monoinfection and co-infections. Spatial variations of co-infection prevalence were observed between and within villages. There was a trend for STH infections to be associated with Plasmodium infection [OR adjusted for age group 1.4, 95% CI (1.0-2.1)], which was more marked for S. stercoralis (OR = 2.2, 95% CI (1.1-4.3). Age and not schooling were risk factors for Plasmodium and STH co-infection. CONCLUSION: The findings suggest that STH and Plasmodium infections tend to occur in the same children, with increasing prevalence of co-infection with age. This calls for an integrated approach such as using mass chemotherapy with dual effect (e.g., ivermectin) coupled with improved housing, sanitation and hygiene for the control of both parasitic infections.

Red blood cell indices and prevalence of hemoglobinopathies and glucose 6 phosphate dehydrogenase deficiencies in male Tanzanian residents of Dar es Salaam.

Hemoglobinopathies, disorders of hemoglobin structure and production, are one of the most common monogenic disorders in humans. Glucose 6 phosphate dehydrogenase deficiency (G6PD) is an inherited enzymopathy resulting in increased oxygen stress susceptibility of red blood cells. The distributions of these genetic traits in populations living in tropical and subtropical regions where malaria has been or is still present are thought to result from survival advantage against severe life threatening malaria disease. 384 male Tanzanian volunteers residing in Dar es Salaam were typed for G6PD, sickle cell disease and α-thalassemia. The most prominent red blood cell polymorphism was heterozygous α(+)-thalassemia (37.8%), followed by the G6PD(A) deficiency (16.4%), heterozygous sickle cell trait (15.9%), G6PD(A-) deficiency (13.5%) and homozygous α(+)-thalassemia (5.2%). 35%, 45%, 17% and 3% of these volunteers were carriers of wild type gene loci, one, two or three of these hemoglobinopathies, respectively. We find that using a cut off value of 28.6 pg. for mean corpuscular hemoglobin (MCH), heterozygous α(+)-thalassemia can be predicted with a sensitivity of 84% and specificity of 72% in this male population. All subjects carrying homozygous α(+)-thalassemia were identified based on their MCH value < 28.6 pg.

Diagnostic accuracy of Kato-Katz, FLOTAC, Baermann, and PCR methods for the detection of light-intensity hookworm and Strongyloides stercoralis infections in Tanzania.

Sensitive diagnostic tools are crucial for an accurate assessment of helminth infections in low-endemicity areas. We examined stool samples from Tanzanian individuals and compared the diagnostic accuracy of a real-time polymerase chain reaction (PCR) with the FLOTAC technique and the Kato-Katz method for hookworm and the Baermann method for Strongyloides stercoralis detection. Only FLOTAC had a higher sensitivity than the Kato-Katz method for hookworm diagnosis; the sensitivities of PCR and the Kato-Katz method were equal. PCR had a very low sensitivity for S. stercoralis detection. The cycle threshold values of the PCR were negatively correlated with the logarithm of hookworm egg and S. stercoralis larvae counts. The median larvae count was significantly lower in PCR false negatives than true positives. All methods failed to detect very low-intensity infections. New diagnostic approaches are needed for monitoring of progressing helminth control programs, confirmation of elimination, or surveillance of disease recrudescence.

Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites.

Controlled human malaria infection (CHMI) by mosquito bite has been used to assess anti-malaria interventions in > 1,500 volunteers since development of methods for infecting mosquitoes by feeding on Plasmodium falciparum (Pf) gametocyte cultures. Such CHMIs have never been used in Africa. Aseptic, purified, cryopreserved Pf sporozoites, PfSPZ Challenge, were used to infect Dutch volunteers by intradermal injection. We conducted a double-blind, placebo-controlled trial to assess safety and infectivity of PfSPZ Challenge in adult male Tanzanians. Volunteers were injected intradermally with 10,000 (N = 12) or 25,000 (N = 12) PfSPZ or normal saline (N = 6). PfSPZ Challenge was well tolerated and safe. Eleven of 12 and 10 of 11 subjects, who received 10,000 and 25,000 PfSPZ respectively, developed parasitemia. In 10,000 versus 25,000 PfSPZ groups geometric mean days from injection to Pf positivity by thick blood film was 15.4 versus 13.5 (P = 0.023). Alpha-thalassemia heterozygosity had no apparent effect on infectivity. PfSPZ Challenge was safe, well tolerated, and infectious.