The impact of soil transmitted helminth on malaria clinical presentation and treatment outcome: A case control study among children in Bagamoyo district, coastal region of Tanzania.

BACKGROUND: Parasitic infectious agents rarely occur in isolation. Epidemiological evidence is mostly lacking, and little is known on how the two common parasites Plasmodium and soil transmitted helminths (STH) interact. There are contradictory findings in different studies. Synergism, antagonism and neutral effect have been documented between Plasmodium and STH. This study investigated the impact of STH on clinical malaria presentation and treatment outcome. METHODS: A matched case control study with a semi longitudinal follow up according to World Health Organization (WHO) antimalarial surveillance guideline was done among children aged 2 months to 9 years inclusively living in western rural areas of Bagamoyo, coastal region of Tanzania. Cases were children with uncomplicated and severe malaria enrolled from the health facilities while controls were children with asymptomatic Plasmodium parasitemia enrolled from the same community. RESULTS: In simple conditional regression analysis there was a tendency for a protective effect of STH on the development of clinical malaria [OR = 0.6, 95% CI of 0.3-1.3] which was more marked for Enterobius vermicularis species [OR = 0.2, 95% CI of 0.0-0.9]. On the contrary, hookworm species tended to be associated with increased risk of clinical malaria [OR = 3.0, 95% CI of 0.9-9.5]. In multiple conditional regression analysis, the overall protective effect was lower for all helminth infection [OR = 0.8, 95% CI of 0.3-1.9] but remained significantly protective for E. vermicularis species [OR = 0.1, 95% CI of 0.0-1.0] and borderline significant for hookworm species [OR = 3.6, 95% CI of 0.9-14.3]. Using ordinal logistic regression which better reflects the progression of asymptomatic Plasmodium parasitemia to severe malaria, there was a 50% significant protective effect with overall helminths [OR = 0.5, 95% CI of 0.3-0.9]. On the contrary, hookworm species was highly predictive of uncomplicated and severe malaria [OR = 7.8, 95% (CI of 1.8-33.9) and 49.7 (95% CI of 1.9-1298.9) respectively]. Generally, children infected with STH had higher geometric mean time to first clearance of parasitemia. CONCLUSION: The findings of a protective effect of E. vermicularis and an enhancing effect of hookworms may explain the contradictory results found in the literature about impact of helminths on clinical malaria. More insight should be gained on possible mechanisms for these opposite effects. These results should not deter at this stage deworming programs but rather foster implementation of integrated control program for these two common parasites.

Occupational exposure to malaria, leishmaniasis and arbovirus vectors in endemic regions: A systematic review.

Vector-borne diseases, including dengue, leishmaniasis and malaria, may be more common among individuals whose occupations or behaviours bring them into frequent contact with these disease vectors outside of their homes. A systematic review was conducted to ascertain at-risk occupations and situations that put individuals at increased risk of exposure to these disease vectors in endemic regions and identify the most suitable interventions for each exposure. The review was conducted in accordance with PRISMA guidelines on articles published between 1945 and October 2021, searched in 16 online databases. The primary outcome was incidence or prevalence of dengue, leishmaniasis or malaria. The review excluded ecological and qualitative studies, abstracts only, letters, commentaries, reviews, and studies of laboratory-acquired infections. Studies were appraised, data extracted, and a descriptive analysis conducted. Bite interventions for each risk group were assessed. A total of 1170 articles were screened and 99 included. Malaria, leishmaniasis and dengue were presented in 47, 41 and 24 articles, respectively; some articles presented multiple conditions. The most represented populations were soldiers, 38% (43 of 112 studies); refugees and travellers, 15% (17) each; migrant workers, 12.5% (14); miners, 9% (10); farmers, 5% (6); rubber tappers and missionaries, 1.8% (2) each; and forest workers, 0.9% (1). Risk of exposure was categorised into round-the-clock or specific times of day/night dependent on occupation. Exposure to these vectors presents a critical and understudied concern for outdoor workers and mobile populations. When devising interventions to provide round-the-clock vector bite protection, two populations are considered. First, mobile populations, characterized by their high mobility, may find potential benefits in insecticide-treated clothing, though more research and optimization are essential. Treated clothing offers personal vector protection and holds promise for economically disadvantaged individuals, especially when enabling them to self-treat their clothing to repel vectors. Secondly, semi-permanent and permanent settlement populations can receive a combination of interventions that offer both personal and community protection, including spatial repellents, suitable for extended stays. Existing research is heavily biased towards tourism and the military, diverting attention and resources from vulnerable populations where these interventions are most required like refugee populations as well as those residing in sub-Saharan Africa.

Navigating a stable transition to the age of intelligence: A mental wealth perspective.

In the grand narrative of technological evolution, we are transitioning from the "Age of Information" to the "Age of Intelligence." Rapid advancements in generative artificial intelligence (AI) are set to reshape society, revolutionize industries, and change the nature of work, challenging our traditional understanding of the dynamics of the economy and its relationship with human productivity and societal prosperity. As we brace for this transformative shift, promising advancements in healthcare, education, productivity, and more, there are concerns of large-scale job loss, mental health repercussions, and risks to social stability and democracy. This paper proposes the concept of Mental Wealth as an action framework that supports nations to proactively position themselves for a smooth transition to the Age of Intelligence while fostering economic and societal prosperity.

The effectiveness of community health worker training, equipping, and deployment in reducing COVID-19 infections and deaths in rural Western Kenya: A comparison of two counties.

COVID-19 and other pandemics remain significant threats to population health, particularly in rural settings where health systems are disproportionately weak. There is a lack of evidence on whether trained, equipped, and deployed community health workers (CHWs) can lead to significant reductions in COVID-19 infections and deaths. Our objective was to measure the effectiveness of deploying trained and equipped CHWs in reducing COVID-19 infections and deaths by comparing outcomes in two counties in rural Western Kenya, a setting with limited critical care capacity and limited access to COVID-19 vaccines and oral COVID-19 antivirals. In Siaya, trained CHWs equipped with thermometers, pulse oximeters, and KN95 masks, visited households to convey health information about COVID-19 prevention. They screened, isolated, and referred COVID-19 cases to facilities with oxygen capacity. They measured and digitally recorded vital signs at the household level. In Kisii county, the standard Kenya national COVID-19 protocol was implemented. We performed a comparative analysis of differences in CHW skills, activity, and COVID-19 infections and deaths using district health information system (DHIS2) data. Trained Siaya CHWs were more skilled in using pulse oximeters and digitally reporting vital signs at the household level. The mean number of oxygen saturation measurements conducted in Siaya was 24.19 per COVID-19 infection; and the mean number of temperature measurements per COVID-19 infection was 17.08. Siaya CHWs conducted significantly more household visits than Kisii CHWs (the mean monthly CHW household visits in Siaya was 146,648.5, standard deviation 11,066.5 versus 42,644.5 in Kisii, standard deviation 899.5, p value = 0.01). Deploying trained and equipped CHWs in rural Western Kenya was associated with lower risk ratios for COVID-19 infections and deaths: 0.54, 95% CI [0.48-0.61] and 0.29, CI [0.13-0.65], respectively, consistent with a beneficial effect.

Sporozoite immunization: innovative translational science to support the fight against malaria.

INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving >90% efficacy against Pf infection. This review describes >30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers exposed to Pf in Africa, with licensure for these populations possible within 5 years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives.

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults.

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.8 × 106 or 2.7 × 106 PfSPZ, of PfSPZ Vaccine, or normal saline administered at 8-week intervals in a randomized, double-blind, placebo-controlled trial stratified by age (6-11 months and 1-5, 6-10, 11-17, 18-35, and 36-61 years). All doses were successfully administered. In all, 192/207 injections (93%) in those aged 6-61 years were rated as causing no or mild pain. There were no significant differences in solicited adverse events (AEs) between vaccinees and controls in any age group (P ≥ 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine.

Advancing detection and response capacities for emerging and re-emerging pathogens in Africa.

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.

Participatory approaches for raising awareness among subsistence farmers in Tanzania about the spread of insecticide resistance in malaria vectors and the possible link to improper agricultural pesticide use.

BACKGROUND: Insecticide resistance is a key barrier to long-term malaria control, and it may be exacerbated by poor agricultural pesticide use. Current practices, however, do not link public health and agricultural pesticide use. This study investigated the perspectives of farmers and other stakeholders regarding the integration of agricultural and public health measures to address resistance. Additionally, the feasibility of participatory workshops to increase the farmers' understanding and participation in pesticide stewardship was assessed. METHODS: Four themes were investigated: pesticide awareness, practices, and opinions of; insecticide resistance in malaria vectors; the effectiveness of current malaria prevention tools; and the links between agricultural and public health pesticide usage. Participatory workshops and field training were held with entomologists, farmers, and agricultural specialists, focusing on agro-ecosystem practices related to pest control; and local farmers were involved in live-testing for insecticides resistance of local Anopheles mosquitoes. RESULTS: Most farmers (94%) considered pesticides effective, and nearly half of them (n = 198, 46.4%) could identify and name crop pests and diseases, mostly using local names. Three quarters were unaware of mosquito larvae in their fields, and only 7% considered their fields as potential sources of mosquitoes. Two thirds were uninformed of any effects that agricultural pesticides may have on mosquitoes, and three quarters had never heard of resistance in malaria mosquitoes. Experts from various sectors acknowledged that agricultural pesticides might impact malaria control through increasing resistance. They did, however, emphasize the importance of crop protection and advocated for the use of pesticides sparingly and non-chemical approaches. Farmers learnt how to discriminate between malaria vectors and non-vectors, identify agricultural pests and diseases, choose and use pesticides effectively, and conduct resistance tests during the participatory workshops. CONCLUSION: This study emphasizes the significance of enhancing subsistence farmers' awareness of mosquito ecology as well as merging public health and agricultural pest management measures. Participatory techniques have the potential to raise stakeholder awareness and engagement, resulting in more effective resistance management.

A malaria-free China: global importance and key experience.

Malaria has a worldwide distribution and is the world's deadliest mosquito-borne disease. The goal of malaria elimination is also reflected in the United Nations Sustainable Development Goals and the Global Technical Strategy for Malaria 2016-2030 issued by the World Health Organization (WHO). China succeeded in its malaria elimination programme after being certified as malaria-free by the WHO on 30 June 2021. Therefore, we document some of the key lessons learnt in the course of the malaria elimination effort in China in this special volume, showing how different strategies made elimination feasible in different subregions of China with different epidemiological and socioeconomic characteristics, in order to present strong signals to other malaria-endemic countries that malaria elimination is feasible within one generation.

Diagnostic performance and comparison of ultrasensitive and conventional rapid diagnostic test, thick blood smear and quantitative PCR for detection of low-density Plasmodium falciparum infections during a controlled human malaria infection study in Equatorial Guinea.

BACKGROUND: Progress towards malaria elimination has stagnated, partly because infections persisting at low parasite densities comprise a large reservoir contributing to ongoing malaria transmission and are difficult to detect. This study compared the performance of an ultrasensitive rapid diagnostic test (uRDT) designed to detect low density infections to a conventional RDT (cRDT), expert microscopy using Giemsa-stained thick blood smears (TBS), and quantitative polymerase chain reaction (qPCR) during a controlled human malaria infection (CHMI) study conducted in malaria exposed adults (NCT03590340). METHODS: Blood samples were collected from healthy Equatoguineans aged 18-35 years beginning on day 8 after CHMI with 3.2 × 103 cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ Challenge, strain NF54) administered by direct venous inoculation. qPCR (18s ribosomal DNA), uRDT (Alere™ Malaria Ag P.f.), cRDT [Carestart Malaria Pf/PAN (PfHRP2/pLDH)], and TBS were performed daily until the volunteer became TBS positive and treatment was administered. qPCR was the reference for the presence of Plasmodium falciparum parasites. RESULTS: 279 samples were collected from 24 participants; 123 were positive by qPCR. TBS detected 24/123 (19.5% sensitivity [95% CI 13.1-27.8%]), uRDT 21/123 (17.1% sensitivity [95% CI 11.1-25.1%]), cRDT 10/123 (8.1% sensitivity [95% CI 4.2-14.8%]); all were 100% specific and did not detect any positive samples not detected by qPCR. TBS and uRDT were more sensitive than cRDT (TBS vs. cRDT p = 0.015; uRDT vs. cRDT p = 0.053), detecting parasitaemias as low as 3.7 parasites/µL (p/µL) (TBS and uRDT) compared to 5.6 p/µL (cRDT) based on TBS density measurements. TBS, uRDT and cRDT did not detect any of the 70/123 samples positive by qPCR below 5.86 p/µL, the qPCR density corresponding to 3.7 p/µL by TBS. The median prepatent periods in days (ranges) were 14.5 (10-20), 18.0 (15-28), 18.0 (15-20) and 18.0 (16-24) for qPCR, TBS, uRDT and cRDT, respectively; qPCR detected parasitaemia significantly earlier (3.5 days) than the other tests. CONCLUSIONS: TBS and uRDT had similar sensitivities, both were more sensitive than cRDT, and neither matched qPCR for detecting low density parasitaemia. uRDT could be considered an alternative to TBS in selected applications, such as CHMI or field diagnosis, where qualitative, dichotomous results for malaria infection might be sufficient.

Testing the contextual Interaction theory in a UHC pilot district in South Africa.

BACKGROUND: World-wide, there is growing universal health coverage (UHC) enthusiasm. The South African government began piloting policies aimed at achieving UHC in 2012. These UHC policies have been and are being rolled out in the ten selected pilot districts. Our study explored policy implementation experiences of 71 actors involved in UHC policy implementation, in one South African pilot district using the Contextual Interaction Theory (CIT) lens. METHOD: Our study applied a two-actor deductive theory of implementation, Contextual Interaction Theory (CIT) to analyse 71 key informant interviews from one National Health Insurance (NHI) pilot district in South Africa. The theory uses motivation, information, power, resources and the interaction of these to explain implementation experiences and outcomes. The research question centred on the utility of CIT tenets in explaining the observed implementation experiences of actors and outcomes particularly policy- practice gaps. RESULTS: All CIT central tenets (information, motivation, power, resources and interactions) were alluded to by actors in their policy implementation experiences, a lack or presence of these tenets were explained as either a facilitator or barrier to policy implementation. This theory was found as very useful in explaining policy implementation experiences of both policy makers and facilitators. CONCLUSION: A central tenet that was present in this context but not fully captured by CIT was leadership. Leadership interactions were revealed as critical for policy implementation, hence we propose the inclusion of leadership interactions to the current CIT central tenets, to become motivation, information, power, resources, leadership and interactions of all these.

Detection of asymptomatic malaria in Asian countries: a meta-analysis of diagnostic accuracy.

BACKGROUND: Achieving malaria elimination requires the targeting of the human reservoir of infection, including those patients with asymptomatic infection. The objective was to synthesise evidence on the accuracy of the rapid-onsite diagnostic tests (RDTs) and microscopy for the detection of asymptomatic malaria as part of the surveillance activities in Asian countries. METHODS: This was a meta-analysis of diagnostic test accuracy. Relevant studies that evaluated the diagnostic performance of RDTs and microscopy for detection of asymptomatic malaria were searched in health-related electronic databases. The methodological quality of the studies included was assessed using the QUADAS-2 tool. RESULTS: Ten studies assessing RDT and/or microscopy were identified. The diagnostic accuracies in all these studies were verified by PCR. Overall, the pooled sensitivities of RDT, as well as microscopy for detection of any malaria parasites in asymptomatic participants, were low, while their pooled specificities were almost ideal. For the detection of Plasmodium falciparum, pooled sensitivity by RDT (59%, 95%CI:16-91%) or microscopy (55%, 95%CI: 25-82%) were almost comparable. For detection of Plasmodium vivax, pooled sensitivity of RDT (51%, 95% CI:7-94%) had also the comparable accuracy of microscopy (54%, 95%CI,11-92%). Of note are the wide range of sensitivity and specificity. CONCLUSION: The findings of this meta-analysis suggest that RDTs and microscopy have limited sensitivity and are inappropriate for the detection of asymptomatic Plasmodium infections. Other methods including a combination of PCR-based strategies, Loop-Mediated Isothermal Amplification (LAMP) technique must be considered to target these infections, in order to achieve malaria elimination. However, more data is needed for the wide acceptance and feasibility of these approaches. Studies to explore the role of asymptomatic and sub-patent infections in the transmission of malaria are of critical importance and are recommended.

Multi-Dose Priming Regimens of PfSPZ Vaccine: Safety and Efficacy against Controlled Human Malaria Infection in Equatoguinean Adults.

Plasmodium falciparum sporozoites (PfSPZ) Vaccine is composed of radiation-attenuated, aseptic, purified cryopreserved PfSPZ. Multiple clinical trials empirically assessing two to six doses have shown multi-dose priming (-two to four doses the first week) to be optimal for protection in both 4- and 16-week regimens. In this randomized, double-blind, normal saline (NS), placebo-controlled trial, four groups (G) of 18- to 32-year-old Equatoguineans received multi-dose priming regimens with or without a delayed final dose at 4 or 16 weeks (9 × 105 PfSPZ/dose). The regimens were G1: days 1, 3, 5, 7, and 113; G2: days 1, 3, 5, and 7; G3: days 1, 3, 5, 7, and 29; and G4: days 1, 8, and 29). All doses were 9 × 105 PfSPZ. Tolerability, safety, immunogenicity, and vaccine efficacy (VE) against homologous-controlled human malaria infection (CHMI) 6-7 weeks after vaccination were assessed to down-select the best regimen. All four regimens were safe and well tolerated, with no significant differences in adverse events (AEs) between vaccinees (N = 84) and NS controls (N = 20) or between regimens. Out of 19 controls, 13 developed Pf parasitemia by quantitative polymerase chain reaction (qPCR) after CHMI. Only the vaccine regimen administered on study days 1, 8, and 29 gave significant protection (7/21 vaccinees versus 13/19 controls infected, VE 51.3%, P = 0.03, Barnard's test, two-tailed). There were no significant differences in antibodies against Pf circumporozoite protein (PfCSP), a major SPZ antigen, between protected and nonprotected vaccinees or controls pre-CHMI. The six controls not developing Pf parasitemia had significantly higher antibodies to blood stage antigens Pf exported protein 1 (PfEXP1) and Pf merozoite surface protein 1 (PfMSP1) than the controls who developed parasitemia, suggesting naturally acquired immunity against Pf-limited infections in controls. This study identified a safe, protective, 4-week, multi-dose prime vaccination regimen for assessment in future trials of PfSPZ Vaccine.

Analysis of nucleic acids extracted from rapid diagnostic tests reveals a significant proportion of false positive test results associated with recent malaria treatment.

BACKGROUND: Surveillance programmes often use malaria rapid diagnostic tests (RDTs) to determine the proportion of the population carrying parasites in their peripheral blood to assess the malaria transmission intensity. Despite an increasing number of reports on false-negative and false-positive RDT results, there is a lack of systematic quality control activities for RDTs deployed in malaria surveillance programmes. METHODS: The diagnostic performance of field-deployed RDTs used for malaria surveys was assessed by retrospective molecular analysis of the blood retained on the tests. RESULTS: Of the 2865 RDTs that were collected in 2018 on Bioko Island and analysed in this study, 4.7% had a false-negative result. These false-negative RDTs were associated with low parasite density infections. In 16.6% of analysed samples, masked pfhrp2 and pfhrp3 gene deletions were identified, in which at least one Plasmodium falciparum strain carried a gene deletion. Among all positive RDTs analysed, 28.4% were tested negative by qPCR and therefore considered to be false-positive. Analysing the questionnaire data collected from the participants, this high proportion of false-positive RDTs could be explained by P. falciparum histidine rich protein 2 (PfHRP2) antigen persistence after recent malaria treatment. CONCLUSION: Malaria surveillance depending solely on RDTs needs well-integrated quality control procedures to assess the extent and impact of reduced sensitivity and specificity of RDTs on malaria control programmes.

Rethinking human resources and capacity building needs for malaria control and elimination in Africa.

Despite considerable success in controlling malaria worldwide, progress toward achieving malaria elimination has largely stalled. In particular, strategies to overcome roadblocks in malaria control and elimination in Africa are critical to achieving worldwide malaria elimination goals-this continent carries 94% of the global malaria case burden. To identify key areas for targeted efforts, we combined a comprehensive review of current literature with direct feedback gathered from frontline malaria workers, leaders, and scholars from Africa. Our analysis identified deficiencies in human resources, training, and capacity building at all levels, from research and development to community involvement. Addressing these needs will require active and coordinated engagement of stakeholders as well as implementation of effective strategies, with malaria-endemic countries owning the relevant processes. This paper reports those valuable identified needs and their concomitant opportunities to accelerate progress toward the goals of the World Health Organization's Global Technical Strategy for Malaria 2016-2030. Ultimately, we underscore the critical need to re-think current approaches and expand concerted efforts toward increasing relevant human resources for health and capacity building at all levels if we are to develop the relevant competencies necessary to maintain current gains while accelerating momentum toward malaria control and elimination.