Investigating differences in village-level heterogeneity of malaria infection and household risk factors in Papua New Guinea

Malaria risk is highly heterogeneous. Understanding village and household-level spatial heterogeneity of malaria risk can support a transition to spatially targeted interventions for malaria elimination. This analysis uses data from cross-sectional prevalence surveys conducted in 2014 and 2016 in two villages (Megiar and Mirap) in Papua New Guinea. Generalised additive modelling was used to characterise spatial heterogeneity of malaria risk and investigate the contribution of individual, household and environmental-level risk factors. Following a period of declining malaria prevalence, the prevalence of P. falciparum increased from 11.4 to 19.1% in Megiar and 12.3 to 28.3% in Mirap between 2014 and 2016, with focal hotspots observed in these villages in 2014 and expanding in 2016. Prevalence of P. vivax was similar in both years (20.6% and 18.3% in Megiar, 22.1% and 23.4% in Mirap) and spatial risk heterogeneity was less apparent compared to P. falciparum. Within-village hotspots varied by Plasmodium species across time and between villages. In Megiar, the adjusted odds ratio (AOR) of infection could be partially explained by household factors that increase risk of vector exposure, such as collecting outdoor surface water as a main source of water. In Mirap, increased AOR overlapped with proximity to densely vegetated areas of the village. The identification of household and environmental factors associated with increased spatial risk may serve as useful indicators of transmission hotspots and inform the development of tailored approaches for malaria control

Perustilaselvitys direktiivilaitosten ympäristölupaharkinnassa ja pilaantuneen ympäristön puhdistamista koskevassa sääntelyssä

Tutkielman aiheena on teollisuuspäästödirektiiviin perustuva perustilaselvitys, joka on Suomessa pantu täytäntöön ympäristönsuojelulain kokonaisuudistuksen yhteydessä. Perustilaselvityksellä tarkoitetaan ympäristön tilainventaariota, jolla selvitetään direktiivilaitosten toimintaan liittyvien merkityksellisten vaarallisten aineiden maaperälle ja pohjavedelle aiheuttama muutos. Euroopan komission mukaan perustilaselvitys on työkalu, jonka avulla pilaantuneen ympäristön ennallistamisen tavoitetaso voidaan teollisen toiminnan päätyttyä määrittää. Tutkielman tavoitteena on selvittää perustilaselvityssääntelyn aiheuttama oikeustilan muutos sekä arvioida selvityksen soveltuvuutta suomalaiseen ympäristölupaharkintaan ja pilaantuneita alueita koskevaan sääntelyyn. Tutkielmassa on lyhyesti esitelty muissa jäsenvaltioissa valittuja toimeenpanoratkaisuja ja arvioitu Suomessa valitun implementointiratkaisun onnistumista suhteessa sääntelyn tavoitteisiin. Aineistona on teollisuuspäästödirektiivin ja ympäristönsuojelulakia koskevan hallituksen esityksen lisäksi käytetty perustilaselvitystä koskevia komission ja ympäristöministeriön ohjeita ja soveltuvissa määrin oikeuskirjallisuutta, joka pääsääntöisesti on peräisin ajalta ennen ympäristönsuojelulain voimaantuloa 1.9.2014. Kirjallisuuden on katsottu olevan käyttökelpoista, koska pilaantuneen ympäristön puhdistamista koskeva sääntely on ympäristönsuojelulain kokonaisuudistuksessa säilytetty pääosin ennallaan. Tutkielma on luonteeltaan lainopillinen, ongelmakeskeinen esitys, joka sijoittuu tutkimuskysymystensä, metodologiansa ja tavoitteidensa johdosta ympäristöoikeuden alalle. Tutkielman perusteella voidaan todeta, että perustilaselvityssääntely ei täysin sovellu suomalaisen ympäristön pilaantumista koskevaan sääntely-ympäristöön. Perustilaselvityksen laatimista koskeva sääntely ja ohjeistus on toteutettu teollisuuspäästödirektiivin tavoitteiden mukaisesti, mutta sääntely on tulkinnanvaraista. Perustilan palauttamista koskeva sääntely on perustilasääntelyn ongelmakohta eikä toiminnan lopettamisvaiheeseen liittyvästä menettelystä sen perusteella synny selkeää kuvaa. Perustilaselvityksen laatiminen voi olla vaikea tehtävä, koska toiminnanharjoittajilta edellytetään vaarallisten aineiden maaperälle ja pohjavedelle mahdollisesti aiheuttaman pilaantumisriskin syvällistä arviointia. Selvityksen mahdolliset hyödyt liittyvät sen ympäristönsuojelullisiin vaikutuksiin. Toiminnanharjoittajien selvilläolovelvollisuus korostuu ja perustilaselvitysten avulla saadaan ajantasaista tietoa maaperän ja pohjaveden tilasta. Tietojen avulla ennaltaehkäisymenetelmiä ja parempia tekniikoita voidaan edelleen kehittää. Maaperän ja pohjaveden laatuinventaariona perustilaselvityksen laatiminen tukee alueiden ennallistamista niiden yksilölliset tarpeet huomioivalla tavalla. Selvitys tarjoaa lupaharkinnassa käytettäväksi aikaisempaa kattavamman ympäristön tilaa koskevan aineiston

Achieving development goals for HIV, tuberculosis and malaria in sub-Saharan Africa through integrated antenatal care:Barriers and challenges

BACKGROUND: The global health community is currently transitioning from the Millennium Development Goals (MDGs) to the Sustainable Development Goals (SDGs). Unfortunately, progress towards maternal, newborn and infant health MDGs has lagged significantly behind other key health goals, demanding a renewed global effort in this key health area. The World Health Organization and other institutions heralded integrated antenatal care (ANC) as the best way to address the inter-related health issues of HIV, tuberculosis (TB) and malaria in the high risk groups of pregnant women and infants; integrated ANC services also offer a mechanism to address slow progress towards improved maternal health. DISCUSSION: There is remarkably limited evidence on best practice approaches of program implementation, acceptability and effectiveness for integrated ANC models targeting multiple diseases. Here, we discuss current integrated ANC global guidelines and the limited literature describing integrated ANC implementation and evidence for their role in addressing HIV, malaria and TB during pregnancy in sub-Saharan Africa. We highlight the paucity of data on the effectiveness of integrated ANC models and identify significant structural barriers in the health system (funding, infrastructure, distribution, human resources), the adoption system (limited buy-in from implementers, leadership, governance) and, in the broader context, patient-centred barriers (fear, stigma, personal burdens) and barriers in funding structures. We highlight recommendations for action and discuss avenues for the global health community to develop systems to integrate multiple disease programs into ANC models of care that better address these three priority infectious diseases. SUMMARY: With the current transition to the SDGs and concerns regarding the failure to meet maternal health MDGs, the global health community, researchers, implementers and funding bodies must work together to ensure the establishment of quality operational and implementation research to inform integrated ANC models. It is imperative that the global health community engages in a timely discussion about such implementation innovations and instigates appropriate actions to ensure advances in maternal health are sufficient to meet applicable SDGs

Ozonide Antimalarial Activity in the Context of Artemisinin-Resistant Malaria

The ozonides are one of the most advanced drug classes in the antimalarial development pipeline and were designed to improve on limitations associated with current front-line artemisinin-based therapies. Like the artemisinins, the pharmacophoric peroxide bond of ozonides is essential for activity, and it appears that these antimalarials share a similar mode of action, raising the possibility of cross-resistance. Resistance to artemisinins is associated with Plasmodium falciparum mutations that allow resistant parasites to escape short-term artemisinin-mediated damage (elimination half-life ~1 h). Importantly, some ozonides (e.g., OZ439) have a sustained in vivo drug exposure profile, providing a major pharmacokinetic advantage over the artemisinin derivatives. Here, we describe recent progress made towards understanding ozonide antimalarial activity and discuss ozonide utility within the context of artemisinin resistance

Quantification of the association between malaria in pregnancy and stillbirth:a systematic review and meta-analysis

Background: 2·6 million stillbirths occur annually worldwide. The association between malaria in pregnancy and stillbirth has yet to be comprehensively quantified. We aimed to quantify the association between malaria in pregnancy and stillbirth, and to assess the influence of malaria endemicity on the association. Methods: We did a systematic review of the association between confirmed malaria in pregnancy and stillbirth. We included population-based cross-sectional, cohort, or case-control studies (in which cases were stillbirths or perinatal deaths), and randomised controlled trials of malaria in pregnancy interventions, identified before Feb 28, 2017. We excluded studies in which malaria in pregnancy was not confirmed by PCR, light microscopy, rapid diagnostic test, or histology. The primary outcome was stillbirth. We pooled estimates of the association between malaria in pregnancy and stillbirth using meta-analysis. We used meta-regression to assess the influence of endemicity. The study protocol is registered with PROSPERO, protocol number CRD42016038742. Findings: We included 59 studies of 995 records identified, consisting of 141 415 women and 3387 stillbirths. Plasmodium falciparum malaria detected at delivery in peripheral samples increased the odds of stillbirth (odds ratio [OR] 1·81 [95% CI 1·42–2·30]; I2=26·1%; 34 estimates), as did P falciparum detected in placental samples (OR 1·95 [1·48–2·57]; I2=33·6%; 31 estimates). P falciparum malaria detected and treated during pregnancy was also associated with stillbirth, but to a lesser extent (OR 1·47 [95% CI 1·13–1·92]; 19 estimates). Plasmodium vivax malaria increased the odds of stillbirth when detected at delivery (2·81 [0·77–10·22]; three estimates), but not when detected and treated during pregnancy (1·09 [0·76–1·57]; four estimates). The association between P falciparum malaria in pregnancy and stillbirth was two times greater in areas of low-to-intermediate endemicity than in areas of high endemicity (ratio of ORs 1·96 [95% CI 1·34–2·89]). Assuming all women with malaria are still parasitaemic at delivery, an estimated 20% of the 1 059 700 stillbirths in malaria-endemic sub-Saharan Africa are attributed to P falciparum malaria in pregnancy; the population attributable fraction decreases to 12%, assuming all women with malaria are treated during pregnancy. Interpretation: P falciparum and P vivax malaria in pregnancy both increase stillbirth risk. The risk of malaria-associated stillbirth is likely to increase as endemicity declines. There is a pressing need for context-appropriate, evidence-based interventions for malaria in pregnancy in low-endemicity settings.</p

Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities

Syndromic management of sexually transmissible infections in resource-poor settings:A systematic review with meta-analysis of the abnormal vaginal discharge flowchart for Neisseria gonorrhoea and Chlamydia trachomatis

Background: Syndromic management of sexually transmissible infections is commonly used in resource-poor settings for the management of common STIs; abnormal vaginal discharge (AVD) flowcharts are used to identify and treat cervical infection including Neisseria gonorrhoea and Chlamydia trachomatis. A systematic review and meta-analysis was undertaken to measure the diagnostic test performance of AVD flowcharts, including both World Health Organization (WHO)- and locally-adapted AVD flowcharts. Methods: A systematic search of multiple electronic databases was conducted to locate eligible studies published between 1991 and 2014. Flowcharts were categorised into one of 14 types based on: 1) use of WHO guidelines or locally-adapted versions; 2) use of risk assessment, clinical examination or both; and 3) symptomatic entry. Summary diagnostic performance measures calculated included summary sensitivity, summary specificity and diagnostic odds ratio. Results: Thirty-six studies, including data on 99 flowcharts, were included in the review. Summary sensitivity estimates for WHO flowcharts ranged from 41.2 to 43.6%, and for locally adapted flowcharts from 39.5 to 74.8%. Locally adapted flowcharts performed slightly better than the WHO flowcharts. A difference in performance was not observed between use of risk assessment or clinical examination. The AVD flowchart performed slightly better when it was not restricted to symptomatic women only. Conclusions: There was considerable variation in the performance of the AVD flowchart but overall it was a poor diagnostic tool regardless of whether risk assessment or clinical examination was included, or whether the flowchart was WHO or locally developed. Many women were treated unnecessarily and many women with cervical infection were not detected. We caution against their continued use for management of cervical infection.<br /

Water, sanitation, and hygiene facilities and hygiene practices associated with diarrhea and vomiting in monastic schools, myanmar

Gastrointestinal diseases are major contributors to mortality among children globally, causing one in 10 child deaths. Although most deaths are in children aged ≤ 5 years, the burden of disease in school-aged children is still considerable and contributes to high rates of school absenteeism. This study investigates behavioral and structural risk factors associated with diarrhea and/or vomiting among schoolchildren in Myanmar. Cross-sectional data from a school-based multistage cluster sample of grade 4 and 5 students were analyzed to explore water, sanitation, and hygiene (WASH) facilities and hygiene-related practices of students in monastic schools in Myanmar. The outcome of interest was student self-reported diarrhea and/or vomiting in the past week. Random effects multinomial logistic regression models were used to explore correlates at the student and school level. A total of 2,082 students from 116 schools across eight states/regions were included. Of these, 11% (223) self-reported at least one episode of diarrhea only, 12% (253) at least one episode of vomiting only, and 12% (244) diarrhea and vomiting in the past week. Independent risk factors associated with the outcome included poor availability of handwash stations, no access to a septic tank toilet, inconsistent toilet use, and lower student grade. These findings highlight the importance of having an adequate number of handwash stations for students, the provision of septic tank toilets, and consistent toilet use. Future WASH programs need to target not only the provision of these WASH facilities but also their utilization, particularly among younger school-aged children

Antibody responses to plasmodium falciparum and plasmodium vivax and prospective risk of plasmodium spp. Infection postpartum

Postpartum women may have an altered susceptibility to Plasmodium falciparum and Plasmodium vivax. The relationship between naturally acquired malarial immunity and susceptibility to malaria postpartum is yet to be determined. IgG levels were measured against P. falciparum and P. vivax antigens from delivery in 201 postpartum and 201 nonpregnant controls over 12 weeks. Associations between time-varying antibody levels and time to first microscopically confirmed species-specific infection were determined by Cox regression. Associations between antibody levels and prospective risk of Plasmodium infection were similar in postpartum and control women. A 2-fold increase in P. falciparum antibody levels was associated with increased prospective risk of P. falciparum infection (hazard ratio [HR] range = 1.37–1.94). Antibody levels against most P. vivax antigens displayed no association with prospective risk of P. vivax infection (HR range = 1.02–1.05) with the exception of PvMSP119 antibodies that were weakly associated with prospective risk of P. vivax infection (HR = 1.14 (95% confidence interval = 1.02, 1.28) per 2-fold increase in levels). Associations between antibody levels and prospective risk of infection attenuated when adjusted for documented retrospective exposure. Serology may be a useful tool to predict and monitor women at increased risk of P. falciparum infection postpartum, particularly in the absence of a detailed history of retrospective infections