Acceptability and uptake of oral HIV self-testing among rural community members in Tanzania: a pilot study.

New strategies are needed to improve HIV testing rates in Tanzania, particularly among adult men. We sought to investigate if HIV oral self-testing would increase HIV testing uptake in Tanzanian rural community homes. The study design was a prospective community-randomized pilot study, in two matched villages with similar characteristics (intervention and control villages) Before data collection, we trained village health workers and research assistants for one week. We recruited male and female adults from 50 representative households in each of two villages in eastern Tanzania. We collected data at baseline and we followed-up the enrolled households after a one-month period. There was a high interest in testing for HIV, with all participants from both arms (100%; n = 259) reporting that they would like to test for HIV. After the one-month follow-up, overall, 66.1% (162/245) of study participants reported to have tested for HIV in both arms. In the intervention arm, 97.6% (124/127) reported that they tested for HIV versus in the control arm, 32.2% (38/118) tested for HIV, p-value < 0.001. In Tanzania, we found that availability of HIV self-testing was associated with an enormous increase in HIV testing uptake in a rural population.

What Proportion of East African Refugees Report Musculoskeletal Problems? A Cross-sectional Survey.

BACKGROUND: Musculoskeletal conditions are the leading cause of disability worldwide and disproportionally affect individuals in low-income and middle-income countries. There is a dearth of evidence on musculoskeletal problems among refugees, 74% of whom reside in low-income and middle-income countries. QUESTIONS/PURPOSES: (1) What proportion of refugees in Nyarugusu Camp, Kigoma, western Tanzania, are affected by musculoskeletal problems and what are the characteristics of those individuals? (2) What are the characteristics of these musculoskeletal problems, including their causes, location, and duration? (3) What forms of healthcare do those with musculoskeletal problems seek, including those for both musculoskeletal and nonmusculoskeletal problems? METHODS: We conducted a cross-sectional study among refugees in Nyarugusu Camp, using the Surgeons OverSeas Assessment of Surgical Need tool. The Surgeons OverSeas Assessment of Surgical Need tool is a validated population-based survey tool developed for use in limited-resource settings that is intended to determine the prevalence of surgical disease in a community. It uses a cluster random sampling methodology with house-to-house data collection in the form of a verbal head-to-toe examination that is performed by a trained community healthcare worker. A total of 99% responded, and 3574 records were analyzed. The mean age of respondents was 23 ± 18 years, with under 18 as the most-represented age group (44% [1563]). A total of 57% (2026) of respondents were women, 79% (2802 of 3536) were generally healthy, and 92% (3297 of 3570) had visited a camp medical facility. Only records endorsing musculoskeletal problems (extremity or back) were included in this analysis. Using all refugees surveyed as our denominator and refugees who endorsed a musculoskeletal problem (extremity or back) as the numerator, we calculated the proportion of refugees who endorsed a musculoskeletal problem. We then analyzed the characteristics of those endorsing musculoskeletal problems, including their healthcare-seeking behavior, and the characteristics of the musculoskeletal problems themselves. RESULTS: Among 3574 refugees interviewed, 22% (769) reported musculoskeletal problems, with 17% (609) reporting extremity problems and 7% (266) reporting back problems. Among all people surveyed, 8% (290) reported current extremity problems while 5% (188) reported current back problems. Among those reporting musculoskeletal problems, respondents younger than 18 years were the most-represented age group (28% [169 of 609]) whereas respondents between 30 and 44 years of age were the most-represented age group for back problems (29% [76 of 266]). Wounds from an injury or trauma (24% [133 of 557]) and acquired disability (24% [133 of 557]) were the most-common causes of extremity problems, whereas acquired disability (53% [97 of 184]) followed by a wound not from injury or trauma (25% [45 of 184]) were the most common causes of back problems. Fifty percent (303) of those with extremity problems characterized it as disabling, whereas 76% (203) of those with back problems did. CONCLUSION: Over one of five refugees endorsed musculoskeletal problems, which are most often caused by acquired disease and injury. These musculoskeletal problems are often characterized as disabling, yet only slightly more than half have sought treatment for problems. This warrants further research on care-seeking behavior in this setting, and emphasizes that investing in the spectrum of musculoskeletal health systems, including medical management and rehabilitation services, is critical to decreasing disability caused by musculoskeletal problems. LEVEL OF EVIDENCE: Level IV, prognostic study.

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.).

Untreated Surgical Problems Among East African Refugees: A Cluster Randomized, Cross-Sectional Study.

OBJECTIVE: The goal of this study was to estimate the prevalence of surgical conditions among refugees in East Africa. BACKGROUND: Surgery is a foundational aspect to high functioning health care systems. In the wake of the Lancet Commission on Global Surgery, previous research has focused on defining the burden of surgical conditions in low- and middle-income countries. Despite numbering over 80 million people globally, forced migrant populations have often been neglected from this body of research. METHODS: We administered a validated survey using random cluster sampling to determine surgical need among refugees in western Tanzania. Primary outcome was history or presence of a surgical problem. Analysis included descriptive and multivariable logistic regression including an average marginal effects model. RESULTS: We analyzed data from 3,574 refugee participants in East Africa. A total of 1,654 participants (46.3%) reported a history or presence of at least one problem that may be surgical in nature. Of those 1,654 participants who did report a problem 1,022 participants (61.8%) reported the problem was still ongoing. Multivariable analysis revealed several factors associated with having a surgical problem (increasing age, occupation, illness within past year). CONCLUSION: To our knowledge, this is the first and largest population-based survey in estimating the prevalence of surgical disease among refugees in sub-Saharan Africa. Our results imply that more than one-in-four refugees has an ongoing surgical problem, suggesting over double the burden of surgical need in refugee populations compared to non-refugee settings.

Prevalence of pediatric surgical problems among east African refugees: estimates from a cross-sectional survey using random cluster sampling.

IMPORTANCE: Surgery is a foundational aspect to high functioning health care systems. In the wake of the Lancet Commission on Global Surgery, previous research has focused on defining the burden of surgical conditions among a pediatric population, however these studies often fail to include forced migrant or refugees. The goal of this study was to estimate the prevalence of pediatric surgical conditions among refugees in east Africa. METHODS: We used the previously validated Surgeons OverSeas Assessment of Surgical Need (SOSAS) that utilizes cross-sectional design with random cluster sampling to assess prevalence of surgical disease among participants aged 0 to 18 years in Nyarugusu refugee camp, Tanzania. We used descriptive and multivariable analyses including an average marginal effects model. RESULTS: A total of 1,658 participants were included in the study. The mean age of our sample was 8.3 ± 5.8 years. A total of 841 participants (50.7%) were male and 817 participants (49.3%) were female. A total of 513 (n = 30.9%) reported a history or presence of a problem that may be surgical in nature, and 280 (54.6%) of them reported the problem was ongoing or untreated. Overall, 16.9% had an ongoing problem that may be amenable to surgery. We found that increasing age and recent illness were associated with having a surgical problem on both our multivariable analyses. CONCLUSION: To our knowledge, this is the first and largest study of prevalence of surgical conditions among refugee children in sub-Saharan Africa. We found that over 16% (one-in-six) of refugee children have a problem that may be amenable to surgery. Our results provide a benchmark upon which other studies in conflict or post-conflict zones with refugee or forced migrant populations may be compared.

Role of human Pegivirus infections in whole Plasmodium falciparum sporozoite vaccination and controlled human malaria infection in African volunteers.

BACKGROUND: Diverse vaccination outcomes and protection levels among different populations pose a serious challenge to the development of an effective malaria vaccine. Co-infections are among many factors associated with immune dysfunction and sub-optimal vaccination outcomes. Chronic, asymptomatic viral infections can contribute to the modulation of vaccine efficacy through various mechanisms. Human Pegivirus-1 (HPgV-1) persists in immune cells thereby potentially modulating immune responses. We investigated whether Pegivirus infection influences vaccine-induced responses and protection in African volunteers undergoing whole P. falciparum sporozoites-based malaria vaccination and controlled human malaria infections (CHMI). METHODS: HPgV-1 prevalence was quantified by RT-qPCR in plasma samples of 96 individuals before, post vaccination with PfSPZ Vaccine and after CHMI in cohorts from Tanzania and Equatorial Guinea. The impact of HPgV-1 infection was evaluated on (1) systemic cytokine and chemokine levels measured by Luminex, (2) PfCSP-specific antibody titers quantified by ELISA, (3) asexual blood-stage parasitemia pre-patent periods and parasite multiplication rates, (4) HPgV-1 RNA levels upon asexual blood-stage parasitemia induced by CHMI. RESULTS: The prevalence of HPgV-1 was 29.2% (28/96) and sequence analysis of the 5' UTR and E2 regions revealed the predominance of genotypes 1, 2 and 5. HPgV-1 infection was associated with elevated systemic levels of IL-2 and IL-17A. Comparable vaccine-induced anti-PfCSP antibody titers, asexual blood-stage multiplication rates and pre-patent periods were observed in HPgV-1 positive and negative individuals. However, a tendency for higher protection levels was detected in the HPgV-1 positive group (62.5%) compared to the negative one (51.6%) following CHMI. HPgV-1 viremia levels were not significantly altered after CHMI. CONCLUSIONS: HPgV-1 infection did not alter PfSPZ Vaccine elicited levels of PfCSP-specific antibody responses and parasite multiplication rates. Ongoing HPgV-1 infection appears to improve to some degree protection against CHMI in PfSPZ-vaccinated individuals. This is likely through modulation of immune system activation and systemic cytokines as higher levels of IL-2 and IL17A were observed in HPgV-1 infected individuals. CHMI is safe and well tolerated in HPgV-1 infected individuals. Identification of cell types and mechanisms of both silent and productive infection in individuals will help to unravel the biology of this widely present but largely under-researched virus.

Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults.

BACKGROUND: A vaccine would be an ideal tool for reducing malaria's impact. PfSPZ Vaccine (radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum [Pf] sporozoites [SPZ]) has been well tolerated and safe in >1526 malaria-naive and experienced 6-month to 65-year-olds in the United States, Europe, and Africa. When vaccine efficacy (VE) of 5 doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine was assessed in adults against controlled human malaria infection (CHMI) in the United States and Tanzania and intense field transmission of heterogeneous Pf in Mali, Tanzanians had the lowest VE (20%). METHODS: To increase VE in Tanzania, we increased PfSPZ/dose (9 × 105 or 1.8 × 106) and decreased numbers of doses to 3 at 8-week intervals in a double blind, placebo-controlled trial. RESULTS: All 22 CHMIs in controls resulted in parasitemia by quantitative polymerase chain reaction. For the 9 × 105 PfSPZ group, VE was 100% (5/5) at 3 or 11 weeks (P < .000l, Barnard test, 2-tailed). For 1.8 × 106 PfSPZ, VE was 33% (2/6) at 7.5 weeks (P = .028). VE of dosage groups (100% vs 33%) was significantly different (P = .022). Volunteers underwent repeat CHMI at 37-40 weeks after last dose. 6/6 and 5/6 volunteers developed parasitemia, but time to first parasitemia was significantly longer than controls in the 9 × 105 PfSPZ group (10.89 vs 7.80 days) (P = .039), indicating a significant reduction in parasites in the liver. Antibody and T-cell responses were higher in the 1.8 × 106 PfSPZ group. CONCLUSIONS: In Tanzania, increasing the dose from 2.7 × 105 to 9 × 105 PfSPZ increased VE from 20% to 100%, but increasing to 1.8 × 106 PfSPZ significantly reduced VE. CLINICAL TRIALS REGISTRATION: NCT02613520.

Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. RESULTS: Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. CONCLUSION: Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001.

Prevalence and assessment of malnutrition among children attending the Reproductive and Child Health clinic at Bagamoyo District Hospital, Tanzania.

BACKGROUND: Malnutrition has long been associated with poverty, poor diet and inadequate access to health care, and it remains a key global health issue that both stems from and contributes to ill-health, with 50 % of childhood deaths due to underlying undernutrition. The purpose of this study was to determine the prevalence of malnutrition among children under-five seen at Bagamoyo District Hospital (BDH) and three rural health facilities ranging between 25 and 55 km from Bagamoyo: Kiwangwa, Fukayosi, and Yombo. METHODS: A total of 63,237 children under-five presenting to Bagamoyo District Hospital and the three rural health facilities participated in the study. Anthropometric measures of age, height/length and weight and measurements of mid-upper arm circumference were obtained and compared with reference anthropometric indices to assess nutritional status for patients presenting to the hospital and health facilities. RESULTS: Overall proportion of stunting, underweight and wasting was 8.37, 5.74 and 1.41 % respectively. Boys were significantly more stunted, under weight and wasted than girls (p-value < 0.05). Children aged 24-59 months were more underweight than 6-23 months (p-value = <0.0001). But, there was no statistical significance difference between the age groups for stunting and wasting. Children from rural areas experienced increased rates of stunting, underweight and wasting than children in urban areas (p-value < 0.05). The results of this study concur with other studies that malnutrition remains a problem within Tanzania; however our data suggests that the population presenting to BDH and rural health facilities presented with decreased rates of malnutrition compared to the general population. CONCLUSIONS: Hospital and facility attending populations of under-five children in and around Bagamoyo suffer moderately high rates of malnutrition. Current nutrition programs focus on education for at risk children and referral to regional hospitals for malnourished children. Even though the general population has even greater malnutrition than the population presenting at the hospital, in areas of high malnutrition, hospital-based interventions should also be considered as centralized locations for reaching thousands of malnourished children under-five.

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.

BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).

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.

Clinical performance of an automated reader in interpreting malaria rapid diagnostic tests in Tanzania.

BACKGROUND: Parasitological confirmation of malaria is now recommended in all febrile patients by the World Health Organization (WHO) to reduce inappropriate use of anti-malarial drugs. Widespread implementation of rapid diagnostic tests (RDTs) is regarded as an effective strategy to achieve this goal. However, the quality of diagnosis provided by RDTs in remote rural dispensaries and health centres is not ideal. Feasible RDT quality control programmes in these settings are challenging. Collection of information regarding diagnostic events is also very deficient in low-resource countries. METHODS: A prospective cohort of consecutive patients aged more than one year from both genders, seeking routine care for febrile episodes at dispensaries located in the Bagamoyo district of Tanzania, were enrolled into the study after signing an informed consent form. Blood samples were taken for thick blood smear (TBS) microscopic examination and malaria RDT (SD Bioline Malaria Antigen Pf/Pan™ (SD RDT)). RDT results were interpreted by both visual interpretation and Deki Reader™ device. Results of visual interpretation were used for case management purposes. Microscopy was considered the "gold standard test" to assess the sensitivity and specificity of the Deki Reader interpretation and to compare it to visual interpretation. RESULTS: In total, 1,346 febrile subjects were included in the final analysis. The SD RDT, when used in conjunction with the Deki Reader and upon visual interpretation, had sensitivities of 95.3% (95% CI, 90.6-97.7) and 94.7% (95% CI, 89.8-97.3) respectively, and specificities of 94.6% (95% CI, 93.5-96.1) and 95.6% (95% CI, 94.2-96.6), respectively to gold standard. There was a high percentage of overall agreement between the two methods of interpretation. CONCLUSION: The sensitivity and specificity of the Deki Reader in interpretation of SD RDTs were comparable to previous reports and showed high agreement to visual interpretation (>98%). The results of the study reflect the situation in real practice and show good performance characteristics of Deki Reader on interpreting malaria RDTs in the hands of local laboratory technicians. They also suggest that a system like this could provide great benefits to the health care system. Further studies to look at ease of use by community health workers, and cost benefit of the system are warranted.

Comparison of bioavailability between the most available generic tablet formulation containing artemether and lumefantrine on the Tanzanian market and the innovator's product.

BACKGROUND: Existence of anti-malarial generic drugs with low bioavailability marketed on sub-Saharan Africa raises a concern on patients achieving therapeutic concentrations after intake of such products. This work compared bioavailability of one generic tablet formulation with innovator's product. Both were fixed dose combination tablet formulations containing artemether and lumefantrine. METHODOLOGY: The study was conducted in Dar Es Salaam, Tanzania, in which a survey of the most abundant generic containing artemether-lumefantrine tablet formulation was carried out in retail pharmacies. The most widely available generic (Artefan®, Ajanta Pharma Ltd, Maharashtra, India) was sampled for bioavailability comparison with Coartem® (Novartis Pharma, Basel, Switzerland)--the innovator's product. A randomized, two-treatment cross-over study was conducted in 18 healthy Tanzanian black male volunteers. Each volunteer received Artefan® (test) and Coartem® (as reference) formulation separated by 42 days of drug-free washout period. Serial blood samples were collected up to 168 hours after oral administration of a single dose of each treatment. Quantitation of lumefantrine plasma levels was done using HPLC with UV detection. Bioequivalence of the two products was assessed in accordance with the US Food and Drug Authority (FDA) guidelines. RESULTS: The most widely available generic in pharmacies was Artefan® from India. All eighteen enrolled volunteers completed the study and both test and reference tablet formulations were well tolerated. It was possible to quantify lumefantrine alone, therefore, the pharmacokinetic parameters reported herein are for lumefantrine. The geometric mean ratios for Cmax, AUC0-t and AUC0-∞ were 84% in all cases and within FDA recommended bioequivalence limits of 80%-125%, but the 90% confidence intervals were outside FDA recommended limits (CI 49-143%, 53-137%, 52-135% respectively). There were no statistical significant differences between the two formulations with regard to PK parameters (P > 0.05). CONCLUSIONS: Although the ratios of AUCs and Cmax were within the acceptable FDA range, bioequivalence between Artefan® and Coartem® tablet formulations was not demonstrated due to failure to comply with the FDA 90% confidence interval criteria. Based on the observed total drug exposure (AUCs), Artefan® is likely to produce a similar therapeutic response as Coartem®.

Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02(D) malaria vaccine in infants living in a malaria-endemic region.

BACKGROUND: The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02(D) vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20 months of follow up. METHODS: This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02(D) or hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. RESULTS: From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02(D) (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18 months after completion of vaccination, 71.8% of recipients of RTS,S/AS02(D) and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02(D) and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02(D) group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p = 0.072) and 26.7% (95% CI: -33.1 to 59.6, p = 0.307) over 12 and 18 months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p = 0.545). CONCLUSIONS: The acceptable safety profile and good tolerability of RTS,S/AS02(D) in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20 month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02(D) group remained significantly higher compared to control for the study duration. Over 18 months follow up, RTS,S/AS02(D) prevented approximately a quarter of malaria cases in the study population. CLINICAL TRIALS: Gov identifier: NCT00289185.

Access to Health Services Among Forced Migrants in Tanzania: A Cluster Randomized Cross Sectional Study of 3560 Congolese and Burundian Refugees.

Despite significant advances in the understanding of the global burden of surgical disease, limited research focuses on access to health and surgical services among refugees, especially in east Africa. The goal of this study was to describe patterns of access to transportation to health services among Congolese and Burundian refugees in Tanzania. We utilized cluster random sampling to perform a large, cross-sectional study in Nyarugusu refugee camp, Tanzania using an adapted version of the Surgeon Overseas Assessment Tool (SOSAS). We randomly selected 132 clusters out of 1472 clusters, randomly selected two people from all households in those clusters. Data analysis was performed in STATA (Stata Version 16, College Station, TX). A total of 3560 participants were included in the study including 1863 Congolese refugees and 1697 Burundian refugees. The majority of refugees reported they were generally healthy (n = 2792, 79.3%). The most common period of waiting to be seen at the health center was between three and 5 h (n = 1502, 45.8%), and over half of all refugees waited between 3 and 12 h to be seen. There was heterogeneity in other intra-camp referral networks (e.g. to and from traditional healer and hospital). Finally, a low percentage (3%) of participants reported leaving the refugee camp to seek health care elsewhere, and Congolese refugees were more likely to pursue self-referral in this manner. To our knowledge, this is the largest study focused on access to transportation among refugees in Tanzania and sub-Saharan Africa. Most participants reported financial difficulty always affording transportation costs with significant wait times occurring once arrived at the hospital. Our study does suggest that some independent health care seeking did occur outside of the camp-based services. Future research may focus more specifically on barriers to timely servicing of patients and patterns of self-referral.Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author 1 Given name: [Zachary Obinna] Last Name [Enumah] and Author 2 Given name: [Mohamed Yunus] Last Name [Rafiq]. Also, kindly confirm the details in the metadata are correct.Confirmed.

Reasons for referral and referral compliance among Congolese and Burundian refugees living in Tanzania: a community-based, cross-sectional survey.

OBJECTIVES: In order to prevent overburdening of higher levels of care, national healthcare systems rely on processes of referral, including for refugee populations which number 26 million globally. The goal of this study is to use data from a population-based household survey to describe patterns of referral services among a population of Congolese and Burundian refugees living in Tanzania. DESIGN: Cross-sectional survey using cluster randomised sampling. SETTING: Nyarugusu refugee camp, Kigoma, Tanzania. PARTICIPANTS: 153 refugees. PRIMARY OUTCOME: Referral compliance. SECONDARY OUTCOMES: Proportion of referrals that were surgical; proportion of referrals requiring diagnostic imaging. RESULTS: Out of 153 individuals who had been told they needed a referral, 96 (62.7%) had gone to the referral hospital. Of the 57 who had not gone, 36 (63%) reported they were still waiting to go and had waited over a month. Of the participants who had been referred (n=96), almost half of the participants reported they were referred for a surgical problem (n=43, 45%) and the majority received radiological testing at an outside hospital (n=72, 75%). Congolese refugees more frequently had physically completed their referral compared with Burundians (Congolese: n=68, 76.4% vs Burundian: n=28, 43.8%, p<0.001). In terms of intracamp referral networks, most refugees reported being referred to the hospital or clinic by a community health worker (n=133, 86.9%). CONCLUSION: To our knowledge, this is the first community-based study on patterns of referral healthcare among refugees in Tanzania and sub-Saharan Africa. Our findings suggest patients were referred for surgical problems and for imaging, however not all referrals were completed in a timely fashion. Future research should attempt to build prospective referral registries that allow for better tracking of patients and examination of waiting times.

Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants.

BACKGROUND: The RTS,S/AS malaria vaccine is being developed for delivery through the World Health Organization's Expanded Program on Immunization (EPI). We assessed the feasibility of integrating RTS,S/AS02D into a standard EPI schedule for infants. METHODS: In this phase 2B, single-center, double-blind, controlled trial involving 340 infants in Bagamoyo, Tanzania, we randomly assigned 340 infants to receive three doses of either the RTS,S/AS02D vaccine or the hepatitis B vaccine at 8, 12, and 16 weeks of age. All infants also received a vaccine containing diphtheria and tetanus toxoids, whole-cell pertussis vaccine, and conjugated Haemophilus influenzae type b vaccine (DTPw/Hib). The primary objectives were the occurrence of serious adverse events during a 9-month surveillance period and a demonstration of noninferiority of the responses to the EPI vaccines (DTPw/Hib and hepatitis B surface antigen) with coadministration of the RTS,S/AS02D vaccine, as compared with the hepatitis B vaccine. The detection of antibodies against Plasmodium falciparum circumsporozoite and efficacy against malaria infection were secondary objectives. RESULTS: At least one serious adverse event was reported in 31 of 170 infants who received the RTS,S/AS02D vaccine (18.2%; 95% confidence interval [CI], 12.7 to 24.9) and in 42 of 170 infants who received the hepatitis B vaccine (24.7%; 95% CI, 18.4 to 31.9). The results showed the noninferiority of the RTS,S/AS02D vaccine in terms of antibody responses to EPI antigens. One month after vaccination, 98.6% of infants receiving the RTS,S/AS02D vaccine had seropositive titers for anticircumsporozoite antibodies on enzyme-linked immunosorbent assay (ELISA). During the 6-month period after the third dose of vaccine, the efficacy of the RTS,S/AS02D vaccine against first infection with P. falciparum malaria was 65.2% (95% CI, 20.7 to 84.7; P=0.01). CONCLUSIONS: The use of the RTS,S/AS02D vaccine in infants had a promising safety profile, did not interfere with the immunologic responses to coadministered EPI antigens, and reduced the incidence of malaria infection. (ClinicalTrials.gov number, NCT00289185.)

Challenges of establishing a Community Advisory Board (CAB) in a low-income, low-resource setting: experiences from Bagamoyo, Tanzania.

OBJECTIVE: Community Advisory Boards are now seen as standard practice for clinical vaccine and drug trials worldwide. In the past, most Community Advisory Boards (CABs) were established by activists and lobbyists to monitor HIV/AIDS vaccine and drug trials in developed countries. In Africa the first CAB was established in Uganda in 1990 in conjunction with an HIV vaccine project and has since been followed by others in South Africa, Zimbabwe, and Kenya. In 2007, the Bagamoyo branch of the Ifakara Health Institute initiated the formation of a CAB. The aim was to properly educate and empower elected CAB members to become full partners in all research activities concerning the public within the Bagamoyo area. METHODS AND RESULTS: Beginning in 2007, staff visited each of the 24 villages within the study area to inform the communities about the proposed CAB and asked them to elect two individuals to represent their village on the CAB. The first attempt was hampered by community leaders selecting themselves, which led to inconsistent attendance, gender imbalance, and political infighting. New criteria for the selection of representatives were implemented to exclude governmental leaders, illiterate representatives and to promote a one-to-one gender balance. The newly appointed representatives underwent training and have participated in CAB meetings largely devoid of the negative issues previously encountered. CONCLUSION: The successfully established CAB has led to improved relations with the community and facilitated the recruitment of study subjects. Our experiences show that, it is possible to establish a non-specific CAB in a low-income setting.

Safety and Differential Antibody and T-Cell Responses to the Plasmodium falciparum Sporozoite Malaria Vaccine, PfSPZ Vaccine, by Age in Tanzanian Adults, Adolescents, Children, and Infants.

In 2016, there were more cases and deaths caused by malaria globally than in 2015. An effective vaccine would be an ideal additional tool for reducing malaria's impact. Sanaria® PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ) has been well tolerated and safe in malaria-naïve and experienced adults in the United States and Mali and protective against controlled human malaria infection with Pf in the United States and field transmission of Pf in Mali, but had not been assessed in younger age groups. We, therefore, evaluated PfSPZ Vaccine in 93 Tanzanians aged 45 years to 6 months in a randomized, double-blind, normal saline placebo-controlled trial. There were no significant differences in adverse events between vaccinees and controls or between dosage regimens. Because all age groups received three doses of 9.0 × 105 PfSPZ of PfSPZ Vaccine, immune responses were compared at this dosage. Median antibody responses against Pf circumsporozoite protein and PfSPZ were highest in infants and lowest in adults. T-cell responses were highest in 6-10-year olds after one dose and 1-5-year olds after three doses; infants had no significant positive T-cell responses. The safety data were used to support initiation of trials in > 300 infants in Kenya and Equatorial Guinea. Because PfSPZ Vaccine-induced protection is thought to be mediated by T cells, the T-cell data suggest PfSPZ Vaccine may be more protective in children than in adults, whereas infants may not be immunologically mature enough to respond to the PfSPZ Vaccine immunization regimen assessed.