Low Endemic Settings Research Articles

Retrospective active case finding in Cambodia: An innovative approach to leprosy control in a low-endemic country

Currently, leprosy control relies on the clinical diagnosis of leprosy and the subsequent administration of multidrug therapy (MDT). However, many health workers are not familiar with the cardinal signs of leprosy, particularly in low-endemic settings including Cambodia. In response, a new approach to early diagnosis was developed in the country, namely retrospective active case finding (RACF) through small mobile teams. In the frame of RACF, previously diagnosed leprosy patients are traced and their contacts screened through “drives”.According to the available records, 984 of the 1,463 (67.3%) index patients diagnosed between 2001 and 2010 and registered in the national leprosy database were successfully traced in the period 2012–2015. Migration (8.4%), death (6.7%), operational issues (1.6%) and unidentified other issues (16.0%) were the main reasons for non-traceability. A total of 17,134 contacts of traced index patients (average: 2.2 household members and 15.2 neighbors) and another 7,469 contacts of the untraced index patients could be screened. Among them, 264 new leprosy patients were diagnosed. In the same period, 1,097 patients were diagnosed through the routine passive case detection system. No change was observed in the relation between the rate at which new patients were identified and the number of years since the diagnosis of the index patient. Similar to leprosy patients diagnosed through passive case detection, the leprosy patients detected through RACF were predominantly adult males. However, the fraction of PB leprosy patients was higher among the patients diagnosed through RACF, suggesting relatively earlier diagnosis.It appears that RACF is a feasible option and effective in detecting new leprosy patients among contacts of previously registered patients. However, a well-maintained national leprosy database is essential for successful contact tracing. Hence, passive case detection in the frame of routine leprosy surveillance is a precondition for efficient RACF as the two systems are mutually enhancing. Together, the two approaches may offer an interesting option for countries with low numbers of leprosy patients but evidence of ongoing transmission. The impact on leprosy transmission could be further increased by the administration of single dose rifampicin as post-exposure prophylaxis to eligible contacts.

Morbidity of schistosomiasis mansoni in a low endemic setting in Ouro Preto, Minas Gerais, Brazil.

Despite the advances of disease control programs, severe forms of schistosomiasis are prevalent. The prevalence of the disease in areas frequented by tourists urges for permanent prevention and control. The aim of this study was to describe the morbidity of schistosomiasis in the district of Antônio Pereira, Ouro Preto, Minas Gerais, Brazil. The proportion of positives was defined by Kato-Katz coproscopy and urinary POC-CCA rapid test. Hepatosplenic form was diagnosed using abdominal ultrasound. Out of 180 participants,97 were examined by Kato-Katz, with 4 (4.1%) being positive. Thirty-four (22.1%) out of 154 were positive by POC-CCA. Five (2.8%) of 177 examined by ultrasound had hepatosplenic form. One of them had undergone splenectomy. One (0.6%)participant had myeloradiculopathy. Severe forms of schistosomiasis are still prevalent in low endemic areas and should be thoroughly investigated.

MalERA: An updated research agenda for characterising the reservoir and measuring transmission in malaria elimination and eradication.

This paper summarises key advances in defining the infectious reservoir for malaria and the measurement of transmission for research and programmatic use since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid and effective progress towards elimination requires an improved understanding of the sources of transmission as well as those at risk of infection. Characterising the transmission reservoir in different settings will enable the most appropriate choice, delivery, and evaluation of interventions. Since 2011, progress has been made in a number of areas. The extent of submicroscopic and asymptomatic infections is better understood, as are the biological parameters governing transmission of sexual stage parasites. Limitations of existing transmission measures have been documented, and proof-of-concept has been established for new innovative serological and molecular methods to better characterise transmission. Finally, there now exists a concerted effort towards the use of ensemble datasets across the spectrum of metrics, from passive and active sources, to develop more accurate risk maps of transmission. These can be used to better target interventions and effectively monitor progress toward elimination. The success of interventions depends not only on the level of endemicity but also on how rapidly or recently an area has undergone changes in transmission. Improved understanding of the biology of mosquito–human and human–mosquito transmission is needed particularly in low-endemic settings, where heterogeneity of infection is pronounced and local vector ecology is variable. New and improved measures of transmission need to be operationally feasible for the malaria programmes. Outputs from these research priorities should allow the development of a set of approaches (applicable to both research and control programmes) that address the unique challenges of measuring and monitoring transmission in near-elimination settings and defining the absence of transmission.

Utilizing the ultrasensitive Schistosoma up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) assay for sample pooling-strategies

BackgroundMethodological applications of the high sensitivity genus-specific Schistosoma CAA strip test, allowing detection of single worm active infections (ultimate sensitivity), are discussed for efficient utilization in sample pooling strategies. Besides relevant cost reduction, pooling of samples rather than individual testing can provide valuable data for large scale mapping, surveillance, and monitoring.MethodThe laboratory-based CAA strip test utilizes luminescent quantitative up-converting phosphor (UCP) reporter particles and a rapid user-friendly lateral flow (LF) assay format. The test includes a sample preparation step that permits virtually unlimited sample concentration with urine, reaching ultimate sensitivity (single worm detection) at 100% specificity. This facilitates testing large urine pools from many individuals with minimal loss of sensitivity and specificity. The test determines the average CAA level of the individuals in the pool thus indicating overall worm burden and prevalence. When requiring test results at the individual level, smaller pools need to be analysed with the pool-size based on expected prevalence or when unknown, on the average CAA level of a larger group; CAA negative pools do not require individual test results and thus reduce the number of tests.ResultsStraightforward pooling strategies indicate that at sub-population level the CAA strip test is an efficient assay for general mapping, identification of hotspots, determination of stratified infection levels, and accurate monitoring of mass drug administrations (MDA). At the individual level, the number of tests can be reduced i.e. in low endemic settings as the pool size can be increased as opposed to prevalence decrease.ConclusionsAt the sub-population level, average CAA concentrations determined in urine pools can be an appropriate measure indicating worm burden. Pooling strategies allowing this type of large scale testing are feasible with the various CAA strip test formats and do not affect sensitivity and specificity. It allows cost efficient stratified testing and monitoring of worm burden at the sub-population level, ideally for large-scale surveillance generating hard data for performance of MDA programs and strategic planning when moving towards transmission-stop and elimination.

Tuberculous uveitis: association between anti-tuberculous therapy and clinical response in a non-endemic country

BackgroundThe study aims to report the association between successful uveitis control following anti-tuberculous therapy (ATT) for uveitis associated with a positive tuberculosis (TB) screening test in a low endemic setting. A retrospective chart review of cases between 2010 and 2017 at a tertiary uveitis referral center in the United States of America was conducted. Subjects with any form of uveitis, a positive TB interferon-gamma release assay or tuberculin skin test, and negative evaluation for other causes of uveitis were included. ATT was recommended in all cases and completed therapy was categorized as either adequate or inadequate for active TB infection. Location and severity of inflammation and the use of local versus systemic corticosteroid therapy was assessed at presentation and again after recommendation of ATT.ResultsThirty-one eyes of 20 individuals were identified. Uveitis activity improved in 22 eyes of 15 patients (13 treated adequately for active TB, 2 not adequately treated). Nine eyes of 5 patients did not have improved activity (1 adequately treated, 4 not adequately treated). All 9 individuals presenting with posterior or panuveitis who improved were adequately treated whereas the remaining 2 who did not improve were not (P 0.02). Among those with anterior or intermediate uveitis, no clear treatment patterns were observed between those who did and did not improve (P 0.50). Six individuals (30%) experienced significant ATT-related adverse effects.ConclusionsIn a non-endemic setting, ATT for uveitis associated with a positive TB screening test may provide benefit in controlling ocular inflammation, particularly for those with posterior or panuveitis. The role for ATT in anterior or intermediate uveitis is less clear.

Predominance of asymptomatic and sub-microscopic infections characterizes the Plasmodium gametocyte reservoir in the Peruvian Amazon

Malaria transmission requires that Anopheles mosquitoes ingest Plasmodium gametocyte stages circulating in the human bloodstream. In the context of malaria elimination, understanding the epidemiology of gametocytes relative to all Plasmodium infections and the contribution of asymptomatic and sub-microscopic parasite carriers to the gametocyte reservoir is necessary, especially in low endemic settings with predominance of P.vivax. A 13-month longitudinal study was conducted in two communities (n = 1935 individuals) of Loreto Department, Peru, with five active screenings for Plasmodium infections and gametocyte stages by quantitative real-time PCR (qPCR) and reverse transcription (RT)-qPCR, respectively. Parasite prevalence by qPCR was 7.2% for P.vivax (n = 520/7235; range by survey 6.0%-8.1%) and 3.2% for P.falciparum (n = 235/7235; range by survey 0.4%-7.7%). Sub-microscopic infections accounted for 73.5% of P.vivax (range by survey 60%-89%) and almost the totality of P.falciparum cases. Gametocytes were found in 28.4% P.vivax infections (range by survey 18.7%-34.1%), with a peak of 61.5% in one community at the start of the transmission season. About 59.8% of all P.vivax gametocyte carriers were asymptomatic and 31.9% were sub-microscopic. Age patterns for gametocyte prevalence paralleled asexual stage infections and peaked among >15–25 year old individuals. Asexual parasite density was found to be the strongest predictor for P.vivax gametocyte presence in longitudinal multivariate analysis (odds ratio 2.33 [95% confidence interval 1.96, 2.78]; P<0.001). Despite significant differences in seasonality patterns and P.vivax prevalence found at the local scale, sub-microscopic and asymptomatic infections predominate and contribute significantly to the gametocyte reservoir in different communities of the Peruvian Amazon. Control and elimination campaigns need sensitive tools to detect all infections that escape routine malaria surveillance, which may contribute to maintain transmission in the region.

Adherence to Antituberculosis Drugs in Children and Adolescents in A Low-Endemic Setting: A Retrospective Series.

Adherence to antituberculosis drug regimens is critical for the prevention and treatment of tuberculosis in pediatrics. In a large retrospective series of children and adolescents in Barcelona, Spain, completion of treatment was worse among patients treated for latent infection, compared with those treated for active tuberculosis or receiving primary chemoprophylaxis. Toxicity and cultural and language barriers were identified as predictors of nonadherence.

Relationship between exposure to malaria and haemoglobin level of children 2–9 years old in low malaria transmission settings

In the context of reduced transmission of malaria, it is essential to examine the association between exposure to malaria and haemoglobin level. This study measured the Haemoglobin level of children 2–9 years of age and examined its association with malariometric indices. A cross sectional study was conducted, during June 2016, on 763 children 2–9 years old, recruited from ten sites representing different malaria transmission settings in Ethiopia. Haemoglobin concentration was determined using HemoCue analyzer. Malariometric indices (splenomegaly rate, parasite rate and serological marker) were measured. The overall prevalence of anaemia was 17.3% (95% CI: 14.6–19.9) in the study population. Mild, moderate and severe anaemia accounted for 7.3%, 7.2% and 2.8% respectively. Of the children with anaemia (132), only 7 (5.3%) had malaria parasitaemia. The prevalence of malaria parasitaemia was 3.6% (2/56), 9.1% (5/55) and 0.0% (0/21) among children with mild, moderate and severe anaemia, respectively. Malaria reactive antibody and anaemia co-occurred in 3.13% (21/672) of the samples. Seroprevalence and parasitaemia did not have significant association with anaemia (p>0.05). However, splenomegaly was significantly associated with increased risk of anaemia (AOR=14.93; p=0.001). Anaemia was significantly higher among children 2–4 years old (22.2%), and children living in households without any insecticide treated bed net (34.0%). The prevalence of anaemia was lower by 55.0% among children living in households with at least one net (AOR=0.45, 95% CI: 0.21–0.96). Repeated exposure to malaria infections (seropositive) and parasitaemia was less likely to contribute to development of anaemia among children 2–9 years in this study setting. Thus, in low malaria endemic settings, anaemia prevention and control program required to reconsider the historical evidence that suggests malaria is one of the major risk factor for anaemia.

Defining micro-epidemiology for malaria elimination: systematic review and meta-analysis

BackgroundMalaria risk can vary markedly between households in the same village, or between villages, but the determinants of this “micro-epidemiological” variation in malaria risk remain poorly understood. This study aimed to identify factors that explain fine-scale variation in malaria risk across settings and improve definitions and methods for malaria micro-epidemiology.MethodsA systematic review of studies that examined risk factors for variation in malaria infection between individuals, households, clusters, hotspots, or villages in any malaria-endemic setting was conducted. Four databases were searched for studies published up until 6th October 2015. Crude and adjusted effect estimates for risk factors for malaria infection were combined in random effects meta-analyses. Bias was assessed using the Newcastle–Ottawa Quality Assessment Scale.ResultsFrom 743 retrieved records, 51 studies were selected, representing populations comprising over 160,000 individuals in 21 countries, in high- and low-endemicity settings. Sixty-five risk factors were identified and meta-analyses were conducted for 11 risk factors. Most studies focused on environmental factors, especially increasing distance from a breeding site (OR 0.89, 95% CI 0.86–0.92, 10 studies). Individual bed net use was protective (OR 0.63, 95% CI 0.52–0.77, 12 studies), but not household bed net ownership. Increasing household size (OR 1.08, 95% CI 1.01–1.15, 4 studies) and household crowding (OR 1.79, 95% CI 1.48–2.16, 4 studies) were associated with malaria infection. Health seeking behaviour, medical history and genetic traits were less frequently studied. Only six studies examined whether individual-level risk factors explained differences in malaria risk at village or hotspot level, and five studies reported different risk factors at different levels of analysis. The risk of bias varied from low to high in individual studies. Insufficient reporting and comparability of measurements limited the number of meta-analyses conducted.ConclusionsSeveral variables associated with individual-level malaria infection were identified, but there was limited evidence that these factors explain variation in malaria risk at village or hotspot level. Social, population and other factors may confound estimates of environmental risk factors, yet these variables are not included in many studies. A structured framework of malaria risk factors is proposed to improve study design and quality of evidence in future micro-epidemiological studies.

Assessing cervical intraepithelial neoplasia as an indicator disease for HIV in a low endemic setting: a population-based register study.

To analyse whether the prevalence of undiagnosed HIV among (1) all women in Sweden and (2) migrant women, diagnosed with cervical intraepithelial neoplasia grade 2 or worse CIN2+ reaches the threshold of 0.1%, which has been suggested to be cost-effective for HIV testing. Population-based register study. Counties of Stockholm and Gothenburg, Sweden, 1990-2014. All women, born between 1940 and 1990, with at least one cervical cytology or histology registered in the Swedish National Cervical Screening Register (NKCx). Data were collected from the NKCx and the Swedish National HIV register. The proportion of women with undiagnosed HIV among women with CIN2+ compared with women with a normal/mildly abnormal cytology/histology was assessed. Proportion of women with undiagnosed HIV. The proportion of undiagnosed HIV was higher among all women with CIN2+ than among those without CIN2+ : 0.06% (95% CI 0.04-0.08) versus 0.04% (95% CI 0.04-0.04); P=0.017). Among migrant women, the proportion of undiagnosed HIV was higher among those with CIN2+ than among those without [0.30% (95% CI 0.20-0.43) versus 0.08% (95% CI 0.07-0.10); P<0.001] and exceeded 0.1%, suggesting the cost-effectiveness of HIV testing. Women with undiagnosed HIV at the time of CIN2+ had a significantly lower nadir CD4+ T-cell count, as a measure of immunosuppression, compared with women without CIN2+ before HIV diagnosis (median nadir CD4, 95cells/mm3 versus 210 cells/mm3 ; P<0.01). HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+ . HIV testing should be performed in migrant women with unknown HIV status diagnosed with CIN2+ .

The shape of the iceberg: quantification of submicroscopic Plasmodium falciparum and Plasmodium vivax parasitaemia and gametocytaemia in five low endemic settings in Ethiopia

BackgroundThe widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination. This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia.MethodsTwo cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively. Finger prick whole blood and plasma samples were collected. The prevalence and density of P. falciparum and P. vivax parasitaemia and gametocytaemia were determined by 18S rRNA quantitative PCR (qPCR) and pfs25 and pvs25 reverse transcriptase qPCR. Antibodies against blood stage antigens apical membrane antigen-1 (AMA-1) and merozoite surface protein-1 (MSP-119) were measured for both species.ResultsWhilst only 6 infections were detected by microscopy in 881 slides (0.7%), 107 of 845 blood samples (12.7%) were parasite positive by (DNA-based) qPCR. qPCR parasite prevalence between sites and surveys ranged from 3.8 to 19.0% for P. falciparum and 0.0 to 9.0% for P. vivax. The median density of P. falciparum infections (n = 85) was 24.4 parasites/µL (IQR 18.0–34.0) and the median density of P. vivax infections (n = 28) was 16.4 parasites/µL (IQR 8.8–55.1). Gametocyte densities by (mRNA-based) qRT-PCR were strongly associated with total parasite densities for both P. falciparum (correlation coefficient = 0.83, p = 0.010) and P. vivax (correlation coefficient = 0.58, p = 0.010). Antibody titers against P. falciparum AMA-1 and MSP-119 were higher in individuals who were P. falciparum parasite positive in both surveys (p < 0.001 for both comparisons).DiscussionThis study adds to the available evidence on the wide-scale presence of submicroscopic parasitaemia by quantifying submicroscopic parasite densities and concurrent gametocyte densities. There was considerable heterogeneity in the occurrence of P. falciparum and P. vivax infections and serological markers of parasite exposure between the examined low endemic settings in Ethiopia.

Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials

BackgroundNovel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant. MethodsBCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland. The subjects were followed for adverse events and CD4+ T cell responses. ResultsH4:IC31 vaccination was well tolerated with a safety profile consisting of mostly mild to moderate self-limited injection site pain, myalgia, arthralgia, fever and post-vaccination inflammatory reaction at the screening tuberculin skin test injection site. The H4:IC31 vaccine elicited antigen-specific CD4+ T cell proliferation and cytokine production that persisted 18weeks after the last vaccination. CD4+ T cell expansion, IFN-γ production and multifunctional CD4+ Th1 responses were most prominent after two doses of H4:IC31 containing 5, 15, or 50μg of H4 in combination with the 500nmol IC31 adjuvant dose. ConclusionsThe novel TB vaccine candidate, H4:IC31, demonstrated an acceptable safety profile and was immunogenic, capable of triggering multifunctional CD4+ T cell responses in previously BCG-vaccinated healthy individuals. These dose-escalation trials provided evidence that the optimal antigen-adjuvant dose combinations are 5, 15, or 50μg of H4 and 500nmol of IC31.Trial registration: ClinicalTrials.gov, NCT02066428 and NCT02074956.

Bead-based immunoassay allows sub-picogram detection of histidine-rich protein 2 from Plasmodium falciparum and estimates reliability of malaria rapid diagnostic tests.

Detection of histidine-rich protein 2 (HRP2) from the malaria parasite Plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs. Here we present a new HRP2 immunoassay based on antigen capture through a bead-based system capable of detecting HRP2 at sub-picogram levels. The assay is highly specific and cost-effective, allowing fast processing and screening of large numbers of samples. We utilized the assay to assess results of HRP2-based rapid diagnostic tests (RDTs) in different P. falciparum transmission settings, generating estimates for true performance in the field. Through this method of external validation, HRP2 RDTs were found to perform well in the high-endemic areas of Mozambique and Angola with 86.4% and 73.9% of persons with HRP2 in their blood testing positive by RDTs, respectively, and false-positive rates of 4.3% and 0.5%. However, in the low-endemic setting of Haiti, only 14.5% of persons found to be HRP2 positive by the bead assay were RDT positive. Additionally, 62.5% of Haitians showing a positive RDT test had no detectable HRP2 by the bead assay, likely indicating that these were false positive tests. In addition to RDT validation, HRP2 biomass was assessed for the populations in these different settings, and may provide an additional metric by which to estimate P. falciparum transmission intensity and measure the impact of interventions.

MASS DRUG ADMINISTRATION (MDA) INTEGRATED MALARIA ELIMINATION IN A HYPO-ENDEMIC ISLAND IN LAKE VICTORIA, KENYA

BackgroundMass drug administration (MDA) for malaria elimination has been proposed as a feasible weapon especially for low endemicity settings. Nonetheless, the concept has not been tried for hypo-endemic areas of...

Defining Seropositivity Thresholds for Use in Trachoma Elimination Studies.

BackgroundEfforts are underway to eliminate trachoma as a public health problem by 2020. Programmatic guidelines are based on clinical signs that correlate poorly with Chlamydia trachomatis (Ct) infection in post-treatment and low-endemicity settings. Age-specific seroprevalence of anti Ct Pgp3 antibodies has been proposed as an alternative indicator of the need for intervention. To standardise the use of these tools, it is necessary to develop an analytical approach that performs reproducibly both within and between studies.MethodologyDried blood spots were collected in 2014 from children aged 1–9 years in Laos (n = 952) and Uganda (n = 2700) and from people aged 1–90 years in The Gambia (n = 1868). Anti-Pgp3 antibodies were detected by ELISA. A number of visual and statistical analytical approaches for defining serological status were compared.Principal FindingsSeroprevalence was estimated at 11.3% (Laos), 13.4% (Uganda) and 29.3% (The Gambia) by visual inspection of the inflection point. The expectation-maximisation algorithm estimated seroprevalence at 10.4% (Laos), 24.3% (Uganda) and 29.3% (The Gambia). Finite mixture model estimates were 15.6% (Laos), 17.1% (Uganda) and 26.2% (The Gambia). Receiver operating characteristic (ROC) curve analysis using a threshold calibrated against external reference specimens estimated the seroprevalence at 6.7% (Laos), 6.8% (Uganda) and 20.9% (The Gambia) when the threshold was set to optimise Youden’s J index. The ROC curve analysis was found to estimate seroprevalence at lower levels than estimates based on thresholds established using internal reference data. Thresholds defined using internal reference threshold methods did not vary substantially between population samples.ConclusionsInternally calibrated approaches to threshold specification are reproducible and consistent and thus have advantages over methods that require external calibrators. We propose that future serological analyses in trachoma use a finite mixture model or expectation-maximisation algorithm as a means of setting the threshold for ELISA data. This will facilitate standardisation and harmonisation between studies and eliminate the need to establish and maintain a global calibration standard.

Mapping of Schistosoma mansoni in the Nile Delta, Egypt: Assessment of the prevalence by the circulating cathodic antigen urine assay

In line with WHO recommendations on elimination of schistosomiasis, accurate identification of all areas of residual transmission is a key step to design and implement measures aimed at interrupting transmission in low-endemic settings. To this purpose, we assessed the prevalence of active S. mansoni infection in five pilot governorates in the Nile Delta of Egypt by examining schoolchildren (6–15 years) using the Urine-Circulating Cathodic Antigen (Urine-CCA) cassette test; we also carried out the standard Kato-Katz (KK) thick smear, the monitoring and evaluation tool employed by Egypt’s national schistosomiasis control programme. Prevalence rates determined by the Urine-CCA test for all governorates were higher than those determined by KK (p<0.01). Of 35 districts surveyed in the five governorates, S. mansoni infection was detected in 19 districts (54.3%) using KK, and in 31 districts (88.6%) by Urine-CCA (χ2=9.94; P=0.0016). S. mansoni infections were detected by Urine-CCA, but not by KK in 12 districts (34.3%), and infection was not detected by either of the two diagnostic methods in four districts in Qalyubia governorate. Males and higher age-groups have significantly higher Urine-CCA prevalence rates. Based on the findings of the current S. mansoni mapping exercise, authorities of the Ministry of Health and Population (MoHP) adopted a new elimination strategy by readjusting thresholds for mass treatment with praziquantel and targeting all transmission areas. MoHP is now planning to remap in all other endemic governorates using Urine-CCA with the aim of identifying all areas of transmission where the elimination strategy should be applied.

Scaling-up the use of sulfadoxine-pyrimethamine for the preventive treatment of malaria in pregnancy: results and lessons on scalability, costs and programme impact from three local government areas in Sokoto State, Nigeria.

BackgroundIntermittent preventive treatment of malaria in pregnancy with 3+ doses of sulfadoxine-pyrimethamine (IPTp-SP) reduces maternal mortality and stillbirths in malaria endemic areas. Between December 2014 and December 2015, a project to scale up IPTp-SP to all pregnant women was implemented in three local government areas (LGA) of Sokoto State, Nigeria. The intervention included community education and mobilization, household distribution of SP, and community health information systems that reminded mothers of upcoming SP doses. Health facility IPTp-SP distribution continued in three intervention (population 661,606) and one counterfactual (population 167,971) LGAs. During the project lifespan, 31,493 pregnant women were eligible for at least one dose of IPTp-SP.MethodsCommunity and facility data on IPTp-SP distribution were collected in all four LGAs. Data from a subset of 9427 pregnant women, who were followed through 42 days postpartum, were analysed to assess associations between SP dosages and newborn status. Nominal cost and expense data in 2015 Nigerian Naira were obtained from expenditure records on the distribution of SP.ResultsEighty-two percent (n = 25,841) of eligible women received one or more doses of IPTp-SP. The SP1 coverage was 95% in the intervention LGAs; 26% in the counterfactual. Measurable SP3+ coverage was 45% in the intervention and 0% in the counterfactual LGAs. The mean number of SP doses in the intervention LGAs was 2.1; 0.4 in the counterfactual. Increased doses of IPTp-SP were associated with linear increases in newborn head circumference and lower odds of stillbirth. Any antenatal care utilization predicted larger newborn head circumference and lower odds of stillbirth. The cost of delivering three doses of SP, inclusive of the cost of medicines, was US$0.93–$1.20.ConclusionsIt is feasible, safe, and affordable to scale up the delivery of high impact IPTp-SP interventions in low resource malaria endemic settings, where few women access facility-based maternal health services. ClinicalTrials.gov Identifier NCT02758353. Registered 29 April 2016, retrospectively registeredElectronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1578-x) contains supplementary material, which is available to authorized users.

Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting?

Objectives: A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice.Methods: Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD4 nadir on the incidence of active TB was evaluated.Results: Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/μl. Thirty-six percent of incident TB occurred within 14 days after HIV diagnosis.Conclusion: A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir.

Expressed var gene repertoire and variant surface antigen diversity in a shrinking Plasmodium falciparum population

The var gene-encoded erythrocyte membrane protein-1 of Plasmodium falciparum (PfEMP-1) is the main variant surface antigen (VSA) expressed on infected erythrocytes. The rate at which antibody responses to VSA expressed by circulating parasites are acquired depends on the size of the local VSA repertoire and the frequency of exposure to new VSA. Because parasites from areas with declining malaria endemicity, such as the Amazon, typically express a restricted PfEMP-1 repertoire, we hypothesized that Amazonians would rapidly acquire antibodies to most locally circulating VSA. Consistent with our expectations, the analysis of 5878 sequence tags expressed by 10 local P. falciparum samples revealed little PfEMP-1 DBL1α domain diversity. Among the most commonly expressed DBL1α types, 45% were shared by two or more independent parasite lines. Nevertheless, Amazonians displayed major gaps in their repertoire of anti-VSA antibodies, although the breadth of anti-VSA antibody responses correlated positively with their cumulative exposure to malaria. We found little antibody cross-reactivity even when testing VSA from related parasites expressing the same dominant DBL1α types. We conclude that variant-specific immunity to P. falciparum VSAs develops slowly despite the relatively restricted PfEMP-1 repertoire found in low-endemicity settings.

Malaria intervention scale-up in Africa: effectiveness predictions for health programme planning tools, based on dynamic transmission modelling.

BackgroundScale-up of malaria prevention and treatment needs to continue to further important gains made in the past decade, but national strategies and budget allocations are not always evidence-based. Statistical models were developed summarizing dynamically simulated relations between increases in coverage and intervention impact, to inform a malaria module in the Spectrum health programme planning tool.MethodsThe dynamic Plasmodiumfalciparum transmission model OpenMalaria was used to simulate health effects of scale-up of insecticide-treated net (ITN) usage, indoor residual spraying (IRS), management of uncomplicated malaria cases (CM) and seasonal malaria chemoprophylaxis (SMC) over a 10-year horizon, over a range of settings with stable endemic malaria. Generalized linear regression models (GLMs) were used to summarize determinants of impact across a range of sub-Sahara African settings.ResultsSelected (best) GLMs explained 94–97 % of variation in simulated post-intervention parasite infection prevalence, 86–97 % of variation in case incidence (three age groups, three 3-year horizons), and 74–95 % of variation in malaria mortality. For any given effective population coverage, CM and ITNs were predicted to avert most prevalent infections, cases and deaths, with lower impacts for IRS, and impacts of SMC limited to young children reached. Proportional impacts were larger at lower endemicity, and (except for SMC) largest in low-endemic settings with little seasonality. Incremental health impacts for a given coverage increase started to diminish noticeably at above ~40 % coverage, while in high-endemic settings, CM and ITNs acted in synergy by lowering endemicity. Vector control and CM, by reducing endemicity and acquired immunity, entail a partial rebound in malaria mortality among people above 5 years of age from around 5–7 years following scale-up. SMC does not reduce endemicity, but slightly shifts malaria to older ages by reducing immunity in child cohorts reached.ConclusionHealth improvements following malaria intervention scale-up vary with endemicity, seasonality, age and time. Statistical models can emulate epidemiological dynamics and inform strategic planning and target setting for malaria control.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1461-9) contains supplementary material, which is available to authorized users.