Mass testing and treatment for malaria followed by weekly fever screening, testing and treatment in Northern Senegal: feasibility, cost and impact.

BACKGROUND: Population-wide interventions using malaria testing and treatment might decrease the reservoir of Plasmodium falciparum infection and accelerate towards elimination. Questions remain about their effectiveness and evidence from different transmission settings is needed. METHODS: A pilot quasi-experimental study to evaluate a package of population-wide test and treat interventions was conducted in six health facility catchment areas (HFCA) in the districts of Kanel, Linguère, and Ranérou (Senegal). Seven adjacent HFCAs were selected as comparison. Villages within the intervention HFCAs were stratified according to the 2013 incidences of passively detected malaria cases, and those with an incidence ≥ 15 cases/1000/year were targeted for a mass test and treat (MTAT) in September 2014. All households were visited, all consenting individuals were tested with a rapid diagnostic test (RDT), and, if positive, treated with dihydroartemisinin-piperaquine. This was followed by weekly screening, testing and treatment of fever cases (PECADOM++) until the end of the transmission season in January 2015. Villages with lower incidence received only PECADOM++ or case investigation. To evaluate the impact of the interventions over that transmission season, the incidence of passively detected, RDT-confirmed malaria cases was compared between the intervention and comparison groups with a difference-in-difference analysis using negative binomial regression with random effects on HFCA. RESULTS: During MTAT, 89% (2225/2503) of households were visited and 86% (18,992/22,170) of individuals were tested, for a combined 77% effective coverage. Among those tested, 291 (1.5%) were RDT positive (range 0-10.8 by village), of whom 82% were < 20 years old and 70% were afebrile. During the PECADOM++ 40,002 visits were conducted to find 2784 individuals reporting fever, with an RDT positivity of 6.5% (170/2612). The combination of interventions resulted in an estimated 38% larger decrease in malaria case incidence in the intervention compared to the comparison group (adjusted incidence risk ratio = 0.62, 95% CI 0.45-0.84, p = 0.002). The cost of the MTAT was $14.3 per person. CONCLUSIONS: It was operationally feasible to conduct MTAT and PECADOM++ with high coverage, although PECADOM++ was not an efficient strategy to complement MTAT. The modest impact of the intervention package suggests a need for alternative or complementary strategies.

Correction to: Mass testing and treatment for malaria followed by weekly fever screening, testing and treatment in Northern Senegal: feasibility, cost and impact.

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The effect of facility-based antiretroviral therapy programs on outpatient services in Kenya and Uganda.

BACKGROUND: Considerable debate exists concerning the effects of antiretroviral therapy (ART) service scale-up on non-HIV services and overall health system performance in sub-Saharan Africa. In this study, we examined whether ART services affected trends in non-ART outpatient department (OPD) visits in Kenya and Uganda. METHODS: Using a nationally representative sample of health facilities in Kenya and Uganda, we estimated the effect of ART programs on OPD visits from 2007 to 2012. We modeled the annual percent change in non-ART OPD visits using hierarchical mixed-effects linear regressions, controlling for a range of facility characteristics. We used four different constructs of ART services to capture the different ways in which the presence, growth, overall, and relative size of ART programs may affect non-ART OPD services. RESULTS: Our final sample included 321 health facilities (140 in Kenya and 181 in Uganda). On average, OPD and ART visits increased steadily in Kenya and Uganda between 2007 and 2012. For facilities where ART services were not offered, the average annual increase in OPD visits was 4·2% in Kenya and 13·5% in Uganda. Among facilities that provided ART services, we found average annual OPD volume increases of 7·2% in Kenya and 5·6% in Uganda, with simultaneous annual increases of 13·7% and 12·5% in ART volumes. We did not find a statistically significant relationship between annual changes in OPD services and the presence, growth, overall, or relative size of ART services. However, in a subgroup analysis, we found that Ugandan hospitals that offered ART services had statistically significantly less growth in OPD visits than Ugandan hospitals that did not provide ART services. CONCLUSIONS: Our findings suggest that ART services in Kenya and Uganda did not have a statistically significant deleterious effects on OPD services between 2007 and 2012, although subgroup analyses indicate variation by facility type. Our findings are encouraging, particularly given recent recommendations for universal access to ART, demonstrating that expanding ART services is not inherently linked to declines in other health services in sub-Saharan Africa.

Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial.

BACKGROUND: Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS: A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence. RESULTS: All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02-.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06-1.49; P = .14) and 58% lower (0.42; .18-.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point. CONCLUSIONS: Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas. CLINICAL TRIALS REGISTRATION: NCT02329301.

The potential to expand antiretroviral therapy by improving health facility efficiency: evidence from Kenya, Uganda, and Zambia.

BACKGROUND: Since 2000, international funding for HIV has supported scaling up antiretroviral therapy (ART) in sub-Saharan Africa. However, such funding has stagnated for years, threatening the sustainability and reach of ART programs amid efforts to achieve universal treatment. Improving health system efficiencies, particularly at the facility level, is an increasingly critical avenue for extending limited resources for ART; nevertheless, the potential impact of increased facility efficiency on ART capacity remains largely unknown. Through the present study, we sought to quantify facility-level technical efficiency across countries, assess potential determinants of efficiency, and predict the potential for additional ART expansion. METHODS: Using nationally-representative facility datasets from Kenya, Uganda and Zambia, and measures adjusting for structural quality, we estimated facility-level technical efficiency using an ensemble approach that combined restricted versions of Data Envelopment Analysis and Stochastic Distance Function. We then conducted a series of bivariate and multivariate regression analyses to evaluate possible determinants of higher or lower technical efficiency. Finally, we predicted the potential for ART expansion across efficiency improvement scenarios, estimating how many additional ART visits could be accommodated if facilities with low efficiency thresholds reached those levels of efficiency. RESULTS: In each country, national averages of efficiency fell below 50 % and facility-level efficiency markedly varied. Among facilities providing ART, average efficiency scores spanned from 50 % (95 % uncertainty interval (UI), 48-62 %) in Uganda to 59 % (95 % UI, 53-67 %) in Zambia. Of the facility determinants analyzed, few were consistently associated with higher or lower technical efficiency scores, suggesting that other factors may be more strongly related to facility-level efficiency. Based on observed facility resources and an efficiency improvement scenario where all facilities providing ART reached 80 % efficiency, we predicted a 33 % potential increase in ART visits in Kenya, 62 % in Uganda, and 33 % in Zambia. Given observed resources in facilities offering ART, we estimated that 459,000 new ART patients could be seen if facilities in these countries reached 80 % efficiency, equating to a 40 % increase in new patients. CONCLUSIONS: Health facilities in Kenya, Uganda, and Zambia could notably expand ART services if the efficiency with which they operate increased. Improving how facility resources are used, and not simply increasing their quantity, has the potential to substantially elevate the impact of global health investments and reduce treatment gaps for people living with HIV.

Cost-Effectiveness of Focal Mass Drug Administration and Mass Drug Administration with Dihydroartemisinin-Piperaquine for Malaria Prevention in Southern Province, Zambia: Results of a Community-Randomized Controlled Trial.

Community-wide administration of antimalarial drugs in therapeutic doses is a potential tool to prevent malaria infection and reduce the malaria parasite reservoir. To measure the effectiveness and cost of using the antimalarial drug combination dihydroartemisinin-piperaquine (DHAp) through different community-wide distribution strategies, Zambia's National Malaria Control Centre conducted a three-armed community-randomized controlled trial. The trial arms were as follows: 1) standard of care (SoC) malaria interventions, 2) SoC plus focal mass drug administration (fMDA), and 3) SoC plus MDA. Mass drug administration consisted of offering all eligible individuals DHAP, irrespective of a rapid diagnostic test (RDT) result. Focal mass drug administration consisted of offering DHAP to all eligible individuals who resided in a household where anyone tested positive by RDT. Results indicate that the costs of fMDA and MDA per person targeted and reached are similar (US$9.01 versus US$8.49 per person, respectively, P = 0.87), but that MDA was superior in all cost-effectiveness measures, including cost per infection averted, cost per case averted, cost per death averted, and cost per disability-adjusted life year averted. Subsequent costing of the MDA intervention in a non-trial, operational setting yielded significantly lower costs per person reached (US$2.90). Mass drug administration with DHAp also met the WHO thresholds for "cost-effective interventions" in the Zambian setting in 90% of simulations conducted using a probabilistic sensitivity analysis based on trial costs, whereas fMDA met these criteria in approximately 50% of simulations. A sensitivity analysis using costs from operational deployment and trial effectiveness yielded improved cost-effectiveness estimates. Mass drug administration may be a cost-effective intervention in the Zambian context and can help reduce the parasite reservoir substantially. Mass drug administration was more cost-effective in relatively higher transmission settings. In all scenarios examined, the cost-effectiveness of MDA was superior to that of fMDA.

Treatment Coverage Estimation for Mass Drug Administration for Malaria with Dihydroartemisinin-Piperaquine in Southern Province, Zambia.

Mass drug administration (MDA) is currently being considered as an intervention in low-transmission areas to complement existing malaria control and elimination efforts. The effectiveness of any MDA strategy is dependent on achieving high epidemiologic coverage and participant adherence rates. A community-randomized controlled trial was conducted from November 2014 to March 2016 to evaluate the impact of four rounds of MDA or focal MDA (fMDA)-where treatment was given to all eligible household members if anyone in the household had a positive malaria rapid diagnostic test-on malaria outcomes in Southern Province, Zambia (population approximately 300,000). This study examined epidemiologic coverage and program reach using capture-recapture and satellite enumeration methods to estimate the degree to which the trial reached targeted individuals. Overall, it was found that the percentage of households visited by campaign teams ranged from 62.9% (95% CI: 60.0-65.8) to a high of 77.4% (95% CI: 73.8-81.0) across four rounds of treatment. When the maximum number of visited households across all campaign rounds was used as the numerator, program reach for at least one visit would have been 86.4% (95% CI: 80.8-92.0) in MDA and 83.5% (95% CI: 78.0-89.1) in fMDA trial arms. As per the protocol, the trial provided dihydroartemisinin-piperaquine treatment to an average of 58.8% and 13.3% of the estimated population based on capture-recapture in MDA and fMDA, respectively, across the four rounds.

Impact of Four Rounds of Mass Drug Administration with Dihydroartemisinin-Piperaquine Implemented in Southern Province, Zambia.

Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.

Prevalence of Plasmodium falciparum and Non-falciparum Infections by Photo-Induced Electron Transfer-PCR in a Longitudinal Cohort of Individuals Enrolled in a Mass Drug Administration Trial in Southern Province, Zambia.

Malaria burden in Zambia has significantly declined over the last decade because of improved coverage of several key malaria interventions (e.g., vector control, case management, bed net distributions, and enhanced surveillance/responses). Campaign-based mass drug administration (MDA) and focal MDA (fMDA) were assessed in a trial in Southern Province, Zambia, to identify its utility in elimination efforts. As part of the study, a longitudinal cohort was visited and tested (by PCR targeting the 18s rRNA and a Plasmodium falciparum-specific rapid diagnostic test [RDT] from SD Bioline) every month for the trial duration (18 months). Overall, there was high concordance (> 97%) between the PCR and RDT results, using the PCR as the gold standard. The RDTs had high specificity and negative predictive values (98.5% and 98.6%, respectively) but low sensitivity (53.0%) and a low positive predictive value (53.8%). There was evidence for persistent antigenemia affecting the low specificity of the RDT, while false-negative RDTs were associated with a lower parasite density than true positive RDTs. Plasmodium falciparum was the dominant species identified, with 98.3% of all positive samples containing P. falciparum. Of these, 97.5% were mono-infections and 0.8% coinfections with one other species. Plasmodium malariae was found in 1.4% of all positive samples (50% mono-infections and 50% coinfections with P. falciparum), whereas Plasmodium ovale was found in 1.1% of all positive samples (90% mono-infections and 10% coinfections with P. falciparum). Although MDA/fMDA appeared to reduce P. malariae prevalence, P. ovale prevalence appeared unchanged.

Efficiency of Health Care Production in Low-Resource Settings: A Monte-Carlo Simulation to Compare the Performance of Data Envelopment Analysis, Stochastic Distance Functions, and an Ensemble Model.

Low-resource countries can greatly benefit from even small increases in efficiency of health service provision, supporting a strong case to measure and pursue efficiency improvement in low- and middle-income countries (LMICs). However, the knowledge base concerning efficiency measurement remains scarce for these contexts. This study shows that current estimation approaches may not be well suited to measure technical efficiency in LMICs and offers an alternative approach for efficiency measurement in these settings. We developed a simulation environment which reproduces the characteristics of health service production in LMICs, and evaluated the performance of Data Envelopment Analysis (DEA) and Stochastic Distance Function (SDF) for assessing efficiency. We found that an ensemble approach (ENS) combining efficiency estimates from a restricted version of DEA (rDEA) and restricted SDF (rSDF) is the preferable method across a range of scenarios. This is the first study to analyze efficiency measurement in a simulation setting for LMICs. Our findings aim to heighten the validity and reliability of efficiency analyses in LMICs, and thus inform policy dialogues about improving the efficiency of health service production in these settings.