Aina Casellas

Interferon-γ–Inducible Protein 10 (IP-10) as a Screening Tool to Optimize Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings

This is an Open Access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com IP-10 as a Screening Tool to Optimize HIV Viral Load Monitoring in Resource-Interferon-γ–inducible protein-10 is an affordable and easily quantifiable biomarker that can be used to accurately screen individuals on antiretroviral treatment (ART) for detectable viremia, optimizing the use of costly viral load determinations required to monitor ART in low-income countries.

Origin of malaria cases: a 7-year audit of global trends in indigenous and imported cases in relation to malaria elimination

Background Countries in the different stages of pre-elimination, elimination, and prevention of reintroduction are required to report the number of indigenous and imported malaria cases to the World Health Organization (WHO). However, these data have not been systematically analysed at the global level. Objective For the period 2007 to 2013, we aimed to report on 1) the proportion of countries providing data on the origin of malaria cases and 2) the origin of malaria cases in countries classified as being in the stages of pre-elimination, elimination and prevention of reintroduction. Design An observational study using annual data reported through routine health information systems to the WHO Global Malaria Programme between 2007 and 2013. Results For all countries classified as being in pre-elimination, elimination, and prevention of reintroduction in the year 2013, there has been a substantial decrease in the total number of indigenous malaria cases, from more than 15,000 cases reported in 2007 to less than 4,000 cases reported in 2013. However, the total number of imported malaria cases has increased over that time period, from 5,600 imported cases in 2007 to approximately 6,800 in 2013. Conclusions Vigilant monitoring of the numbers of imported and indigenous malaria cases at national and global levels as well as appropriate strategies to target these cases will be critical to achieve malaria eradication.Background Countries in the different stages of pre-elimination, elimination, and prevention of reintroduction are required to report the number of indigenous and imported malaria cases to the World Health Organization (WHO). However, these data have not been systematically analysed at the global level. Objective For the period 2007 to 2013, we aimed to report on 1) the proportion of countries providing data on the origin of malaria cases and 2) the origin of malaria cases in countries classified as being in the stages of pre-elimination, elimination and prevention of reintroduction. Design An observational study using annual data reported through routine health information systems to the WHO Global Malaria Programme between 2007 and 2013. Results For all countries classified as being in pre-elimination, elimination, and prevention of reintroduction in the year 2013, there has been a substantial decrease in the total number of indigenous malaria cases, from more than 15,000 cases reported in 2007 to less than 4,000 cases reported in 2013. However, the total number of imported malaria cases has increased over that time period, from 5,600 imported cases in 2007 to approximately 6,800 in 2013. Conclusions Vigilant monitoring of the numbers of imported and indigenous malaria cases at national and global levels as well as appropriate strategies to target these cases will be critical to achieve malaria eradication.

Identifying Immune Correlates of Protection Against Plasmodium falciparum Through a Novel Approach to Account for Heterogeneity in Malaria Exposure

Background A main criterion to identify malaria vaccine candidates is the proof that acquired immunity against them is associated with protection from disease. The age of the studied individuals, heterogeneous malaria exposure, and assumption of the maintenance of a baseline immune response can confound these associations. Methods Immunoglobulin G/immunoglobulin M (IgG/ IgM) levels were measured by Luminex® in Mozambican children monitored for clinical malaria from birth until 3 years of age, together with functional antibodies. Studied candidates were pre-erythrocytic and erythrocytic antigens, including EBAs/PfRhs, MSPs, DBLs, and novel antigens merely or not previously studied in malaria-exposed populations. Cox regression models were estimated at 9 and 24 months of age, accounting for heterogeneous malaria exposure or limiting follow-up according to the antibodys decay. Results Associations of antibody responses with higher clinical malaria risk were avoided when accounting for heterogeneous malaria exposure or when limiting the follow-up time in the analyses. Associations with reduced risk of clinical malaria were found only at 24 months old, but not younger children, for IgG breadth and levels of IgG targeting EBA140III-V, CyRPA, DBL5ε and DBL3x, together with C1q-fixation activity by antibodies targeting MSP119. Conclusions Malaria protection correlates were identified, only in children aged 24 months old when accounting for heterogeneous malaria exposure. These results highlight the relevance of considering age and malaria exposure, as well as the importance of not assuming the maintenance of a baseline immune response throughout the follow-up. Results may be misleading if these factors are not considered.

Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates

Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. We hypothesized that anti-parasite immunity acquired upon exposure would limit invasion-related gene (IRG) expression and affect the clinical impact of the infection. 11 IRG transcript levels were measured in P. falciparum isolates by RT-PCR, and IgG/IgM against invasion ligands by Luminex®, in 50 Mozambican adults, 25 children with severe malaria (SM) and 25 with uncomplicated malaria (UM). IRG expression differences among groups and associations between IRG expression and clinical/immunologic parameters were assessed. IRG expression diversity was higher in parasites infecting children than adults (p = 0.022). eba140 and ptramp expression decreased with age (p = 0.003 and 0.007, respectively) whereas p41 expression increased (p = 0.022). pfrh5 reduction in expression was abrupt early in life. Parasite density decreased with increasing pfrh5 expression (p < 0.001) and, only in children, parasite density increased with p41 expression (p = 0.007), and decreased with eba175 (p = 0.013). Antibody responses and IRG expression were not associated. In conclusion, IRG expression is associated with age and parasite density, but not with specific antibody responses in the acute phase of infection. Our results confirm the importance of multi-antigen vaccines development to avoid parasite immune escape when tested in malaria-exposed individuals.

IP-10 Levels as an Accurate Screening Tool to Detect Acute HIV Infection in Resource-Limited Settings

Acute HIV infection (AHI) is the period prior to seroconversion characterized by high viral replication, hyper-transmission potential and commonly, non-specific febrile illness. AHI detection requires HIV-RNA viral load (VL) determination, which has very limited access in low-income countries due to restrictive costs and implementation constraints. We sought to identify a biomarker that could enable AHI diagnosis in scarce-resource settings, and to evaluate the feasibility of its implementation. HIV-seronegative adults presenting at the Manhiça District Hospital, Mozambique, with reported-fever were tested for VL. Plasma levels of 49 inflammatory biomarkers from AHI (n = 61) and non-HIV infected outpatients (n = 65) were determined by Luminex and ELISA. IP-10 demonstrated the best predictive power for AHI detection (AUC = 0.88 [95%CI 0.80–0.96]). A cut-off value of IP-10 ≥ 161.6 pg/mL provided a sensitivity of 95.5% (95%CI 85.5–99.5) and a specificity of 76.5% (95%CI 62.5–87.2). The implementation of an IP-10 screening test could avert from 21 to 84 new infections and save from US

Awareness of cervical cancer and willingness to be vaccinated against human papillomavirus in Mozambican adolescent girls

176,609 to US

Hepatitis C prevalence among the migrant population in Spain: A systematic review and meta-analysis

533,467 to the health system per 1,000 tested patients. We conclude that IP-10 is an accurate biomarker to screen febrile HIV-seronegative individuals for subsequent AHI diagnosis with VL. Such an algorithm is a cost-effective strategy to prevent disease progression and a substantial number of further HIV infections.

WATER SUPPLY AND SANITATION CONDITIONS IN RURAL SOUTHERN MOZAMBIQUE AND ITS ASSOCIATION WITH MORBIDITY AND MORTALITY INDICATORS, 2012–2015

Sub-Saharan Africa concentrates the largest burden of cervical cancer worldwide. The introduction of the HPV vaccination in this region is urgent and strategic to meet global health targets. This was a cross-sectional study conducted in Mozambique prior to the first round of the HPV vaccine demonstration programme. It targeted girls aged 10–19 years old identified from schools and households. Face-to-face structured interviews were conducted. A total of 1147 adolescents were enrolled in three selected districts of the country. Most girls [84% (967/1147)] had heard of cervical cancer, while 76% believed that cervical cancer could be prevented. However only 33% (373/1144) of girls recognized having ever heard of HPV. When girls were asked whether they would accept to be vaccinated if a vaccine was available in Mozambique, 91% (1025/1130) answered positively. Girls from the HPV demonstration districts showed higher awareness on HPV and cervical cancer, and willingness to be vaccinated. This study anticipates high acceptability of the HPV vaccine in Mozambique and high awareness about cervical cancer, despite low HPV knowledge. These results highlight that targeted health education programmes are critical for acceptance of new tools, and are encouraging for the reduction of cervical cancer related mortality and morbidity in Mozambique.

Drug Therapy for Rate and Rhythm Control in Nonvalvular Atrial Fibrillation: A Cross-sectional Study With Electronic Health Records in a Primary Care Cohort

INTRODUCTION Spain, which has one of the largest migrant populations in Europe, has committed to eliminating the hepatitis C virus (HCV). The aim of this study was to estimate the prevalence of HCV among migrant groups in Spain, a country of 46 million people, with an estimated HCV-antibody prevalence of 1.7%. METHODS Studies on HCV and migration in Spain were identified by systematically searching three databases from the first records to 30 November 2017, and consulting experts at the Ministry of Health and in the 17 Spanish autonomous communities. A meta-analysis was conducted to determine pooled HCV prevalence for the general migrant population. Prevalences were also calculated for high-risk migrant populations and populations who had undergone hospital screening, stratified by region of origin. RESULTS Out of 243 studies identified, 26 met the eligibility criteria. The meta-analysis of the general migrant population found HCV antibody prevalence to be 1.6%. Migrants originating from European countries, including those at high or moderate risk for HCV, had the highest pooled prevalence (7.1%). In the general migrant population, prevalence was highest among sub-Saharan African migrants (3.1%) and lowest among Latin American migrants (0.2%). CONCLUSION Based on the limited available data, the prevalence among the general migrant population was found to be the same as the general Spanish population. Further research is needed to more accurately determine HCV prevalence for the overall migrant population and specific migrant subpopulations with a higher risk in the country as a whole and in each of Spains 17 autonomous communities.

Erratum to: Poor tuberculosis treatment outcomes in Southern Mozambique (2011-2012)

Background Water, sanitation and hygiene (WASH) are major health determinants, responsible for an estimated world-wide disease burden of 5.7%. However, the debate about the effect of water quality, hygiene and sanitation in preventing diarrhoea is still ongoing. The aim of this study is to describe access to improved water supply and sanitation infrastructure, as defined by the Joint Monitoring Programme, in the Manhiça Health Research Centre (CISM) study area and evaluate its association with morbidity and mortality indicators. Methods We conducted a retrospective cohort study. All children under 15 living in the study area during the period 2012–2015 were included (N=61900). Children were followed up until they moved from the study area, turned 15 or until 2015. Water and sanitation household data were obtained from the CISM demographic surveillance system (DSS) in the Manhiça district, an area of around 2380 km2. Clinical data were obtained from CISMs round-the-clock morbidity surveillance system covering outpatient and hospital admissions at the Manhiça District Hospital (MDH) and rural health posts. A negative binomial regression model using Wald test was performed to assess the minimum community-based incidence rates (MCBIR) for every morbidity-mortality indicator. Results Preliminary data showed that 86% of the children lived at least once in a household with unimproved sanitation facilities, 27% with an unimproved water source. Spatial distribution of unimproved water and sanitation facilities showed to be clustered. Access to unimproved sanitation and water facilities was associated to higher rates of diarrhoea, a significant 30% of diarrhoea rate increase was observed for rivers, lakes and ponds as water sources. Other morbidity indicators (malnutrition, parasitaemia, anaemia) also showed a rate increase with the use of unimproved water and sanitation facilities. Conclusions Obtained results are useful to inform sector-related decision-making processes and ultimately improve access to safe drinking water and sanitation in rural southern Mozambique.