BACKGROUND: Tanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen. Eighteen months later we investigated the HIV viral suppression rates and the factors associated with lack of viral suppression among PLHIV (children and adults) in Tanzania. METHODOLOGY: A cross-sectional survey was conducted from September to December 2020 among PLHIV on antiretroviral therapy (ART) in Tanzania. Whole blood samples, demographic data and clinical information were obtained from eligible adults (≥15 years) and children (< 15 years) attending thirty-six HIV care and treatment centres located in 22 regions of Tanzania mainland. A whole blood sample from each participant was processed into plasma and HIV viral load was estimated using real-time PCR. HIV viral suppression was defined at a cut-off of < 50 copies/mL as recommended by WHO. Analyses were conducted using descriptive statistics to establish the national representative prevalence of viral suppression, and logistic regression analyses to determine independent factors associated with non-suppression. RESULTS: A total of 2,039 PLHIV on ART were recruited; of these, adults and children were 57.5% (n = 1173) and 42.5% (n = 866), respectively. Among the adult population, the mean age and standard deviation (SD) was 42.1 ± 12.4 years, with 64.7% being female. Among children, the mean age and SD were 9.6 ± 3 years, and 53.2% were female. Overall viral suppression at < 50 copies/mL (undetectable) was achieved in 87.8% of adults and 74.4% of children. Adults and children on dolutegravir-based regimen recorded viral suppression rates of 89.7% and 85.1% respectively. Factors independently associated with lack of viral suppression status in the adult population were age and ART adherence while in the children population, the factors were sex, ART adherence, and current ART regimen (p<0.05). CONCLUSION: Dolutegravir-based regimens are promising to help attain epidemic control in Tanzania. More efforts especially on ART adherence are needed to attain optimal treatment outcomes for children and adults PLHIV in Tanzania.

BACKGROUND: There is limited evidence on COVID-19 vaccination uptake among people living with HIV (PLHIV) and health care workers (HCWs), with the current evidence concentrated in high-income countries. There is also limited documentation in the published literature regarding the feasibility and lessons from implementing targeted vaccination strategies to reach PLHIV and HCWs in low- and middle-income countries. PROGRAM DEVELOPMENT, PILOTING, AND IMPLEMENTATION: We designed and implemented multifaceted strategies to scale up targeted COVID-19 vaccination among PLHIV and HCWs in 11 administrative regions on the mainland of Tanzania plus Zanzibar. An initial 6-week intensification strategy was implemented using a diverse partnership model comprising key stakeholders at the national- and subnational levels. A layered package of strategies included expanding the number of certified vaccinators, creating vaccination points within HIV clinics, engaging HCWs to address their concerns, and building the capacity of HCWs as "champions" to promote and facilitate vaccination. We then closely monitored COVID-19 vaccination uptake in 562 high-volume HIV clinics. Between September 2021 and September 2022, the proportion of fully vaccinated adult PLHIV increased from <1% to 97% and fully vaccinated HCWs increased from 23% to 80%. LESSONS AND IMPLICATIONS: Our intra-action review highlighted the importance of leveraging a strong foundation of existing partnerships and platforms, integrating COVID-19 vaccination points within HIV clinics, and refining strategies to increase vaccination demand while ensuring continuity of vaccine supply to meet the increased demand. Lessons from Tanzania can inform targeted vaccination of vulnerable groups in future health emergencies.

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a major contributor to the substantial reductions in global malaria morbidity and mortality over the last decade. In Tanzania, artemether-lumefantrine (AL) was introduced as the first-line treatment for uncomplicated Plasmodium falciparum malaria in 2006. The World Health Organization (WHO) recommends regular assessment and monitoring of the efficacy of the first-line treatment, specifically considering that artemisinin resistance has been confirmed in the Greater Mekong sub-region. This study's main aim was to assess the efficacy and safety of AL for treating uncomplicated P. falciparum malaria in Tanzania. METHODS: This was a single-arm prospective antimalarial drug efficacy trial conducted in four of the eight National Malaria Control Programme (NMCP) sentinel sites in 2019. The trial was carried out in outpatient health facilities in Karume-Mwanza region, Ipinda-Mbeya region, Simbo-Tabora region, and Nagaga-Mtwara region. Children aged six months to 10 years with microscopy confirmed uncomplicated P. falciparum malaria who met the inclusion criteria were recruited based on the WHO protocol. The children received AL (a 6-dose regimen of AL twice daily for three days). Clinical and parasitological parameters were monitored during follow-up over 28 days to evaluate drug efficacy. RESULTS: A total of 628 children were screened for uncomplicated malaria, and 349 (55.6%) were enrolled between May and September 2019. Of the enrolled children, 343 (98.3%) completed the 28-day follow-up or attained the treatment outcomes. There were no early treatment failures; recurrent infections during follow-up were common at two sites (Karume 29.5%; Simbo 18.2%). PCR-corrected adequate clinical and parasitological response (ACPR) by survival analysis to AL on day 28 of follow-up varied from 97.7% at Karume to 100% at Ipinda and Nagaga sites. The commonly reported adverse events were cough, skin pallor, and abdominal pain. The drug was well tolerated, and no serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria in Tanzania in 2019. The high recurrent infections were mainly due to new infections, highlighting the potential role of introducing alternative artemisinin-based combinations that offer improved post-treatment prophylaxis, such as artesunate-amodiaquine (ASAQ).

BACKGROUND: The use of artemisinin-based combination therapy (ACT) is recommended by the World Health Organization for the treatment of uncomplicated falciparum malaria. Artemether-lumefantrine (AL) is the most widely adopted first-line ACT for uncomplicated malaria in sub-Saharan Africa (SSA), including mainland Tanzania, where it was introduced in December 2006. The WHO recommends regular assessment to monitor the efficacy of the first-line treatment specifically considering that artemisinin partial resistance was reported in Greater Mekong sub-region and has been confirmed in East Africa (Rwanda and Uganda). The main aim of this study was to assess the efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in mainland Tanzania. METHODS: A single-arm prospective anti-malarial drug efficacy trial was conducted in Kibaha, Mlimba, Mkuzi, and Ujiji (in Pwani, Morogoro, Tanga, and Kigoma regions, respectively) in 2018. The sample size of 88 patients per site was determined based on WHO 2009 standard protocol. Participants were febrile patients (documented axillary temperature ≥ 37.5 °C and/or history of fever during the past 24 h) aged 6 months to 10 years. Patients received a 6-dose AL regimen by weight twice a day for 3 days. Clinical and parasitological parameters were monitored during 28 days of follow-up to evaluate the drug efficacy and safety. RESULTS: A total of 653 children were screened for uncomplicated malaria and 349 (53.7%) were enrolled between April and August 2018. Of the enrolled children, 345 (98.9%) completed the 28 days of follow-up or attained the treatment outcomes. There were no early treatment failures, but recurrent infections were higher in Mkuzi (35.2%) and Ujiji (23%). By Kaplan-Meier analysis of polymerase chain reaction (PCR) uncorrected adequate clinical and parasitological response (ACPR) ranged from 63.4% in Mkuzi to 85.9% in Mlimba, while PCR-corrected ACPR on day 28 varied from 97.6% in Ujiji to 100% in Mlimba. The drug was well tolerated; the commonly reported adverse events were cough, runny nose, and abdominal pain. No serious adverse event was reported. CONCLUSION: This study showed that AL had adequate efficacy and safety for the treatment of uncomplicated falciparum malaria. The high number of recurrent infections were mainly due to new infections, indicating the necessity of utilizing alternative artemisinin-based combinations, such as artesunate amodiaquine, which provide a significantly longer post-treatment prophylactic effect.

Plasmodium falciparum with the histidine rich protein 2 gene (pfhrp2) deleted from its genome can escape diagnosis by HRP2-based rapid diagnostic tests (HRP2-RDTs). The World Health Organization (WHO) recommends switching to a non-HRP2 RDT for P. falciparum clinical case diagnosis when pfhrp2 deletion prevalence causes ≥ 5% of RDTs to return false negative results. Tanzania is a country of heterogenous P. falciparum transmission, with some regions approaching elimination and others at varying levels of control. In concordance with the current recommended WHO pfhrp2 deletion surveillance strategy, 100 health facilities encompassing 10 regions of Tanzania enrolled malaria-suspected patients between February and July 2021. Of 7863 persons of all ages enrolled and providing RDT result and blood sample, 3777 (48.0%) were positive by the national RDT testing for Plasmodium lactate dehydrogenase (pLDH) and/or HRP2. A second RDT testing specifically for the P. falciparum LDH (Pf-pLDH) antigen found 95 persons (2.5% of all RDT positives) were positive, though negative by the national RDT for HRP2, and were selected for pfhrp2 and pfhrp3 (pfhrp2/3) genotyping. Multiplex antigen detection by laboratory bead assay found 135/7847 (1.7%) of all blood samples positive for Plasmodium antigens but very low or no HRP2, and these were selected for genotyping as well. Of the samples selected for genotyping based on RDT or laboratory multiplex result, 158 were P. falciparum DNA positive, and 140 had sufficient DNA to be genotyped for pfhrp2/3. Most of these (125/140) were found to be pfhrp2+/pfhrp3+, with smaller numbers deleted for only pfhrp2 (n = 9) or only pfhrp3 (n = 6). No dual pfhrp2/3 deleted parasites were observed. This survey found that parasites with these gene deletions are rare in Tanzania, and estimated that 0.24% (95% confidence interval: 0.08% to 0.39%) of false-negative HRP2-RDTs for symptomatic persons were due to pfhrp2 deletions in this 2021 Tanzania survey. These data provide evidence for HRP2-based diagnostics as currently accurate for P. falciparum diagnosis in Tanzania.

Social network strategy (SNS) testing uses network connections to refer individuals at high risk to HIV testing services (HTS). In Tanzania, SNS testing is offered in communities and health facilities. In communities, SNS testing targets key and vulnerable populations (KVP), while in health facilities it complements index testing by reaching unelicited index contacts. Routine data were used to assess performance and trends over time in PEPFAR-supported sites between October 2021 and March 2023. Key indicators included SNS social contacts tested, and new HIV-positives individuals identified. Descriptive and statistical analysis were conducted. Univariable and multivariable analysis were applied, and variables with P-values <0.2 at univariable analysis were considered for multivariable analysis. Overall, 121,739 SNS contacts were tested, and 7731 (6.4%) previously undiagnosed individuals living with HIV were identified. Tested contacts and identified HIV-positives were mostly aged ≥15 years (>99.7%) and females (80.6% of tests, 79.4% of HIV-positives). Most SNS contacts were tested (78,363; 64.7%) and diagnosed (6376; 82.5%) in communities. SNS tests and HIV-positives grew 11.5 and 6.1-fold respectively, from October-December 2021 to January-March 2023, with majority of clients reached in communities vs. facilities (78,763 vs. 42,976). These results indicate that SNS testing is a promising HIV case-finding approach in Tanzania.

BACKGROUND: Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. METHODS: A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). RESULTS: Sequencing success was ≥ 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. CONCLUSION: This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Background Despite recent reports of false negative results among histidine-rich protein 2 (HRP2) based-malaria rapid diagnostic tests (mRDTs) caused by pfhrp2/3 gene deletions in different countries, there is paucity of data in Tanzania.Methods This study assessed the status of pfhrp2/3 deletions in 7,543 blood samples using laboratory multiplex antigen detection (Plasmodium lactate dehydrogenase - pLDH, aldolase, and HRP2). Samples showing mRDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped for pfhrp2/3genes.Results Of all samples, 2,417 (32.0%) were positive for any Plasmodium antigens while 5,126 (68.0%) were negative. About 99.8% (n=2,411) of antigen positive samples had HRP2, but 6 (0.2%) had only pLDH and/or pAldolase. Thirteen samples had atypical relationships between pan-Plasmodium antigens and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 mRDTs but positive by microscopy were also chosen; all giving 35 samples genotyped for pfhrp2/3. Of 35 samples, 4 (11.4%) failed to consistently amplify positive control genes (pfmsp1 and pfmsp2), and pfhrp2 and pfhrp3 genes were successfully amplified in 31 (88.6%) samples.Conclusions Lack of pfhrp2 and/or pfhrp3 genes deletions in Plasmodium falciparum parasites supports continued use of HRP2-based mRDTs for routine malaria diagnosis in Tanzania.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe field component of this study was supported by The Global Fund through National Malaria Control Programme of the Tanzanian Ministry of Health. The CDC laboratory work was supported by Malaria Branch and Catherine Bakari’s MSc studies was funded by the Developing Excellence in Leadership and Genomics for Malaria Elimination (DELGEME) project with funding from the Developing Excellence in Leadership and Training (DELTAS) Africa Initiative, of the African Academy of Sciences (AAS).Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request

BACKGROUND: The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. METHODS: Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher's exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. FINDINGS: We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). CONCLUSIONS: VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.

BACKGROUND: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. OBJECTIVES: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. METHODS: A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. RESULTS: HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. CONCLUSIONS: More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) based on the detection of the Plasmodium falciparum histidine-rich protein 2 (HRP2) antigen are widely used for detection of active infection with this parasite and are the only practical malaria diagnostic test in some endemic settings. External validation of RDT results from field surveys can confirm appropriate RDT performance. METHODS: A community-based cross-sectional survey was conducted between July and November 2017 enrolling participants of all ages in households from 15 villages in four border regions of Tanzania: Geita, Kigoma, Mtwara and Ruvuma. All participants had an RDT performed in the field and provided a blood sample for later laboratory multiplex antigen detection of HRP2. In assessing the continuous HRP2 levels in participant blood versus RDT result, dose-response logistic regression provided quantitative estimates for HRP2 limit of detection (LOD). RESULTS: From the 15 study villages, 6941 persons were enrolled that had a RDT at time of enrollment and provided a DBS for later laboratory antigen detection. RDT positive prevalence for the HRP2 band by village ranged from 20.0 to 43.6%, but the magnitude of this prevalence did not have an effect on the estimated LOD of RDTs utilized in different villages. Overall, HRP2 single-target tests had a lower LOD at the 95% probability of positive RDT (4.3 ng/mL; 95% CI 3.4-5.4) when compared to pLDH/HRP2 dual target tests (5.4 ng/mL; 4.5-6.3), though this difference was not significant. With the exception of one village, all other 14 villages (93.3%) showed RDT LOD estimates at 90% probability of positive RDT between 0.5 and 12.0 ng/mL. CONCLUSIONS: Both HRP2-only and pLDH/HRP2 combo RDTs utilized in a 2017 Tanzania cross-sectional survey of border regions generally performed well, and reliably detected HRP2 antigen in the low ng/mL range. Though single target tests had lower levels of HRP2 detection, both tests were within similar ranges among the 15 villages. Comparison of quantitative HRP2 detection limits among study sites can help interpret RDT testing results when generating population prevalence estimates for malaria infection.

INTRODUCTION: Population-based biomarker surveys are the gold standard for estimating HIV prevalence but are susceptible to substantial non-participation (up to 30%). Analytical missing data methods, including inverse-probability weighting (IPW) and multiple imputation (MI), are biased when data are missing-not-at-random, for example when people living with HIV more frequently decline participation. Heckman-type selection models can, under certain assumptions, recover unbiased prevalence estimates in such scenarios. METHODS: We pooled data from 142,706 participants aged 15-49 years from nationally representative cross-sectional Population-based HIV Impact Assessments in seven countries in sub-Saharan Africa, conducted between 2015 and 2018 in Tanzania, Uganda, Malawi, Zambia, Zimbabwe, Lesotho and Eswatini. We compared sex-stratified HIV prevalence estimates from unadjusted, IPW, MI and selection models, controlling for household and individual-level predictors of non-participation, and assessed the sensitivity of selection models to the copula function specifying the correlation between study participation and HIV status. RESULTS: In total, 84.1% of participants provided a blood sample to determine HIV serostatus (range: 76% in Malawi to 95% in Uganda). HIV prevalence estimates from selection models diverged from IPW and MI models by up to 5% in Lesotho, without substantial precision loss. In Tanzania, the IPW model yielded lower HIV prevalence estimates among males than the best-fitting copula selection model (3.8% vs. 7.9%). CONCLUSIONS: We demonstrate how HIV prevalence estimates from selection models can differ from those obtained under missing-at-random assumptions. Further benefits include exploration of plausible relationships between participation and outcome. While selection models require additional assumptions and careful specification, they are an important tool for triangulating prevalence estimates in surveys with substantial missing data due to non-participation.

BACKGROUND: Mobile women are at risk of HIV infection in sub-Saharan Africa, though we lack evidence for HIV risk among women in mobile partnerships, especially in the context of household food insecurity, a growing concern in the region. SETTING: Women aged 15-59 years with a cohabitating male partner and who participated in Population-based HIV Impact Assessment surveys in Eswatini, Lesotho, Namibia, Tanzania, Uganda, and Zambia. METHODS: We evaluated the association between women's and their partner's mobility (being away from home for over one month or staying elsewhere) and transactional sex (selling sex or receiving money or goods in exchange for sex). We examined associations for effect measure modification by food insecurity level in the household in the past month. We used survey-weighted logistic regression, pooled and by country, adjusting for individual, partner and household-level variables. RESULTS: Among women with a cohabitating male partner, 8.0% reported transactional sex, ranging from 2.7% in Lesotho to 13.4% in Uganda. Women's mobility (aOR 1.35 [95% CI 1.08 - 1.68]), but not their partner's mobility (aOR 0.91 [0.74 - 1.12]), was associated with transactional sex. Food insecurity was associated with transactional sex independent of mobility (aOR 1.29 [1.10 - 1.52]). Among those who were food insecure, mobility was not associated with an increased odds of transactional sex. CONCLUSION: Food insecurity and women's mobility each increased the odds of transactional sex. Since transactional sex is associated with HIV risk, prevention programs can address the needs of mobile and food-insecure women, including those in cohabitating relationships.

BACKGROUND: Histidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania. METHODS: A community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes. RESULTS: Of all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes. CONCLUSIONS: This study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future.

In August 2014, the World Health Organization declared the Ebola virus disease epidemic in West Africa a public health emergency of international concern. After 2 imported cases of the disease were identified in the United States in autumn 2014, the Centers for Disease Control and Prevention recommended that all jurisdictions begin active monitoring of travelers at risk of developing Ebola virus disease for 21 days from the last day of a potential exposure to minimize the risk of disease transmission. Here we describe the infrastructure development, monitoring processes, total planned expenditures, and effects on the public health system in Georgia associated with active monitoring and illness response of all travelers from Ebola-affected West African countries from October 2014 to March 2016. We conducted qualitative interviews with Georgia Department of Public Health (GDPH) staff. We identified state active monitoring and illness response infrastructure investments and monitoring activities and state and federal funds spent in both areas. And, we evaluated whether active monitoring and illness response enhanced Georgia's ability to respond to future infectious disease outbreaks. Developing the infrastructure to support the monitoring and response required investment in information technology, training of public health and medical personnel, increasing laboratory capacity, and securing personal protective equipment. Estimated total expenditures were $8.25 million, with 76% spent on infrastructure and 17% on daily monitoring. The GDPH leveraged internal resources and partnerships to implement active monitoring and illness response. Infrastructure investment increased surveillance capacity, strengthened relationships between the GDPH and medical providers, and led to the creation of infectious disease transport and hospital networks. Active monitoring and illness response increased outbreak preparedness, but it warrants comparison with other possible responses to determine its overall value.

We estimated the economic impact of concurrent measles and rubella outbreaks in Romania during 2011-2012. We collected costs from surveys of 428 case-patients and caretakers, government records, and health staff interviews. We then estimated financial and opportunity costs. During the study period, 12,427 measles cases and 24,627 rubella cases were recorded; 27 infants had congenital rubella syndrome (CRS). The cost of the outbreaks was US $9.9 million. Cost per case was US $439 for measles, US $132 for rubella, and US $44,051 for CRS. Up to 36% of households needed to borrow money to pay for illness treatment. Approximately 17% of patients continued to work while ill to pay their treatment expenses. Our key study findings were that households incurred a high economic burden compared with their incomes, the health sector bore most costs, and CRS costs were substantial and relevant to include in rubella outbreak cost studies.

Since 1979, multiple CDC Kenya programs have supported the development of diagnostic expertise and laboratory capacity in Kenya. In 2004, CDC's Global Disease Detection (GDD) program within the Division of Global Health Protection in Kenya (DGHP-Kenya) initiated close collaboration with Kenya Medical Research Institute (KEMRI) and developed a laboratory partnership called the Diagnostic and Laboratory Systems Program (DLSP). DLSP built onto previous efforts by malaria, human immunodeficiency virus (HIV) and tuberculosis (TB) programs and supported the expansion of the diagnostic expertise and capacity in KEMRI and the Ministry of Health. First, DLSP developed laboratory capacity for surveillance of diarrheal, respiratory, zoonotic and febrile illnesses to understand the etiology burden of these common illnesses and support evidenced-based decisions on vaccine introductions and recommendations in Kenya. Second, we have evaluated and implemented new diagnostic technologies such as TaqMan Array Cards (TAC) to detect emerging or reemerging pathogens and have recently added a next generation sequencer (NGS). Third, DLSP provided rapid laboratory diagnostic support for outbreak investigation to Kenya and regional countries. Fourth, DLSP has been assisting the Kenya National Public Health laboratory-National Influenza Center and microbiology reference laboratory to obtain World Health Organization (WHO) certification and ISO15189 accreditation respectively. Fifth, we have supported biosafety and biosecurity curriculum development to help Kenyan laboratories safely and appropriately manage infectious pathogens. These achievements, highlight how in collaboration with existing CDC programs working on HIV, tuberculosis and malaria, the Global Health Security Agenda can have significantly improve public health in Kenya and the region. Moreover, Kenya provides an example as to how laboratory science can help countries detect and control of infectious disease outbreaks and other public health threats more rapidly, thus enhancing global health security.

BACKGROUND: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance. METHODS: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively. RESULTS: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene. CONCLUSION: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies. Trial Registration ClinicalTrials.gov NCT03387631.

Background: Hepatitis B affects 257 million people worldwide. Mother-to-child hepatitis B virus (HBV) transmission is a preventable cause of substantial morbidity and mortality and poses greatest risk for developing chronic HBV infection. The World Health Organization recommends that all countries institute universal hepatitis B birth dose (HepB BD) vaccination during the first 24 h of life, followed by timely completion of routine immunization. The objective of this analysis was to assess the cost-effectiveness of adding HepB BD vaccination among sub-Saharan African refugee populations where the host country's national immunization policy includes HepB BD. Methods: We performed a cost-effectiveness analysis of three hepatitis B vaccination strategy scenarios for camp-based refugee populations in the African Region (AFR): routine immunization (RI), RI plus universal HepB BD, and RI plus HepB BD only for newborns of hepatitis B surface antigen-positive mothers identified through rapid diagnostic testing (RDT). We focused analyses on refugee populations living in countries that include HepB BD in national immunization schedules: Djibouti, Algeria and Mauritania. We used a decision tree model to estimate costs of vaccination and testing, and costs of life-years lost due to complications of chronic hepatitis B. Results: Compared with RI alone, addition of HepB BD among displaced Somali refugees in Djibouti camps would save 9807 life-years/year, with an incremental cost-effectiveness ratio (ICER) of 0.15 USD (US dollars) per life-year saved. The RI plus HepB BD strategy among Western Saharan refugees in Algerian camps and Malian refugees in Mauritania camps would save 27,108 life-years/year with an ICER of 0.11 USD and 18,417 life-years/year with an ICER of 0.16 USD, respectively. The RI plus RDT-directed HepB BD was less cost-effective than RI plus delivery of universal HepB BD vaccination or RI alone. Conclusions: Based on our model, addition of HepB BD vaccination is very cost-effective among three sub-Saharan refugee populations, using relative life-years saved. This analysis shows the potential benefit of implementing HepB BD vaccination among other camp-based refugee populations as more AFR countries introduce national HepB BD policies.

The devastating 2010 cholera epidemic in Haiti prompted the government to introduce oral cholera vaccine (OCV) in two high-risk areas of Haiti. We evaluated the direct costs associated with the government's first vaccine campaign implemented in August-September 2013. We analyzed data for major cost categories and assessed the efficiency of available campaign resources to vaccinate the target population. For a target population of 107,906 persons, campaign costs totaled $624,000 and 215,295 OCV doses were dispensed. The total vaccine and operational cost was $2.90 per dose; vaccine alone cost $1.85 per dose, vaccine delivery and administration $0.70 per dose, and vaccine storage and transport $0.35 per dose. Resources were greater than needed-our analyses suggested that approximately 2.5-6 times as many persons could have been vaccinated during this campaign without increasing the resources allocated for vaccine delivery and administration. These results can inform future OCV campaigns in Haiti.

BACKGROUND: With 71% of Malawians living on < $1.90 a day, high household costs associated with severe malaria are likely a major economic burden for low income families and may constitute an important barrier to care seeking. Nevertheless, few efforts have been made to examine these costs. This paper describes household costs associated with seeking and receiving inpatient care for malaria in health facilities in Malawi. METHODS: A cross-sectional survey was conducted in a representative nationwide sample of 36 health facilities providing inpatient treatment for malaria from June-August, 2012. Patients admitted at least 12 h before study team visits who had been prescribed an antimalarial after admission were eligible to provide cost information for their malaria episode, including care seeking at previous health facilities. An ingredients-based approach was used to estimate direct costs. Indirect costs were estimated using a human capital approach. Key drivers of total household costs for illness episodes resulting in malaria admission were assessed by fitting a generalized linear model, accounting for clustering at the health facility level. RESULTS: Out of 100 patients who met the eligibility criteria, 80 (80%) provided cost information for their entire illness episode to date and were included: 39% of patients were under 5 years old and 75% had sought care for the malaria episode at other facilities prior to coming to the current facility. Total household costs averaged $17.48 per patient; direct and indirect household costs averaged $7.59 and $9.90, respectively. Facility management type, household distance from the health facility, patient age, high household wealth, and duration of hospital stay were all significant drivers of overall costs. CONCLUSIONS: Although malaria treatment is supposed to be free in public health facilities, households in Malawi still incur high direct and indirect costs for malaria illness episodes that result in hospital admission. Finding ways to minimize the economic burden of inpatient malaria care is crucial to protect households from potentially catastrophic health expenditures.

Fever is a major cause of morbidity and mortality among children under 5 years of age in resource-limited countries. Although prevention and treatment of febrile illnesses have improved, the costs-both financial and nonfinancial-remain barriers to care. Using data from the 2009 Uganda Malaria Indicator Survey, we describe the costs associated with the care of a febrile child and assess predictors of care-seeking behavior. Over 80% of caregivers sought care for their febrile child, however less than half did so on either the day of or the day after the development of fever. The odds of seeking care decreased with each additional month of the child's age. Caregivers living in rural areas were more likely to seek care, however were less likely to seek care promptly. Caregivers with at least a primary school education and those familiar with the protective effect of bed nets and the need to seek care promptly were more likely to seek care. Despite government assistance, the majority of caregivers did incur costs (mean 13,173 Ugandan shilling; $6.84 U.S. dollars) associated with medical care. Continued efforts targeting barriers to seeking care, including the economic burden, are necessary.

Malaria imposes a substantial global disease burden. It disproportionately affects sub-Saharan Africans, particularly young children. In an effort to improve disease management, the World Health Organization (WHO) recommended in 2010 that countries test children younger than age five who present with suspected malaria fever to confirm the diagnosis instead of treating them presumptively with antimalarial drugs. Costs and concerns about the overall health impact of such diagnostic testing for malaria in children remain barriers to full implementation. Using data from national Malaria Indicator Surveys, we estimated two-stage microsimulation models for Angola, Tanzania, and Uganda to assess the policy's cost-effectiveness. We found that diagnostic testing for malaria in children younger than five is cost-saving in Angola. In Tanzania and Uganda the cost per life-year gained is $5.54 and $94.28, respectively. The costs projected for Tanzania and Uganda are less than the WHO standard of $150 per life-year gained. Our results were robust under varying assumptions about cost, prevalence of malaria, and behavior, and they strongly suggest the pursuit of policies that facilitate full implementation of testing for malaria in children younger than five.

The relationship between maternal education and child health has intrigued researchers for decades. This study explored the interaction between maternal education and childhood malaria infection. Cross-sectional survey data from three African countries were used. Descriptive analysis and multivariate logistic regression models were completed in line with identified correlates. Marginal effects and Oaxaca decomposition analysis on maternal education and childhood malaria infection were also estimated. Children with mothers whose education level was beyond primary school were 4.7% less likely to be malaria-positive (P < 0.001). The Oaxaca decomposition analysis exhibited an 8% gap in childhood malaria infection for educated and uneducated mothers. Over 60% of the gap was explained by differences in household wealth (26%), household place of domicile (21%), malaria transmission intensities (14%), and media exposure (12%). All other correlates accounted for only 27%. The full adjusted model showed a robust and significant relationship between maternal education and childhood malaria infection.

BACKGROUND: Anti-malarial regimens containing sulphonamide or artemisinin ingredients are widely used in malaria-endemic countries. However, evidence of the incidence of adverse drug reactions (ADR) to these drugs is limited, especially in Africa, and there is a complete absence of information on the economic burden such ADR place on patients. This study aimed to document ADR incidence and associated household costs in three high malaria transmission districts in rural Tanzania covered by demographic surveillance systems. METHODS: Active and passive surveillance methods were used to identify ADR from sulphadoxine-pyrimethamine (SP) and artemisinin (AS) use. ADR were identified by trained clinicians at health facilities (passive surveillance) and through cross-sectional household surveys (active surveillance). Potential cases were followed up at home, where a complete history and physical examination was undertaken, and household cost data collected. Patients were classified as having 'possible' or 'probable' ADR by a physician. RESULTS: A total of 95 suspected ADR were identified during a two-year period, of which 79 were traced, and 67 reported use of SP and/or AS prior to ADR onset. Thirty-four cases were classified as 'probable' and 33 as 'possible' ADRs. Most (53) cases were associated with SP monotherapy, 13 with the AS/SP combination (available in one of the two areas only), and one with AS monotherapy. Annual ADR incidence per 100,000 exposures was estimated based on 'probable' ADR only at 5.6 for AS/SP in combination, and 25.0 and 11.6 for SP monotherapy. Median ADR treatment costs per episode ranged from US$2.23 for those making a single provider visit to US$146.93 for patients with four visits. Seventy-three per cent of patients used out-of-pocket funds or sold part of their farm harvests to pay for treatment, and 19% borrowed money. CONCLUSION: Both passive and active surveillance methods proved feasible methods for anti-malarial ADR surveillance, with active surveillance being an important complement to facility-based surveillance, given the widespread practice of self-medication. Household costs associated with ADR treatment were high and potentially catastrophic. Efforts should be made to both improve pharmacovigilance across Africa and to identify strategies to reduce the economic burden endured by households suffering from ADR.

OBEJCTIVE: To assess the degree to which policy changes to artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria translate into effective ACT delivery. METHODS: Prospective observational study of drug dispensing practices at baseline and during the 3 years following introduction of ACT with sulfadoxine-pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first-line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1 month per quarter, documenting a total of 271 953 patient encounters in the three districts. RESLTS: In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP + AS during the intervention period. Of patients who received SP + AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. CONCLUSIONS: The uptake of SP + AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.