Prevalence and risk factors associated with malaria infection in children under two years of age in southern Togo prior to perennial malaria chemoprevention implementation.

BACKGROUND: Malaria remains the leading cause of mortality and morbidity in young children in sub-Saharan Africa. To prevent malaria in children living in moderate-to-high malaria transmission areas, the World Health Organization has recommended perennial malaria chemoprevention (PMC). Prior to piloting PMC implementation in southern Togo, a household survey was conducted to estimate malaria infection prevalence in children under 2 years of age (U2). METHODS: A cross-sectional community-based household survey was conducted in the Haho district in the Togo Plateaux region. A three-stage random sampling method was used to select study participants aged 10-23 months whose caretakers gave informed consent. The prevalence of Plasmodium infection, defined as a positive rapid diagnostic test (RDT), was estimated with 95% confidence interval (CI). Clinical malaria was defined as having a positive RDT plus fever (≥ 37.5 °C) or history of fever in the last 24 h. Mixed-effects logistic regression models were used to assess the child's, caretaker's, and household's factors associated with malaria infection. RESULTS: A total of 685 children were included in the survey conducted January-February in 2022 (dry season). Median age was 17 months (interquartile range: 13-21). About 80% of the children slept under a bed net the night before the interview. Malaria infection prevalence was 32.1% (95% CI 27.7-37.0) with significant area variation (cluster range: 0.0-73.3). Prevalence of clinical malaria was 15.4% (95% CI 12.2-19.2). Children whose caretakers were animist (aOR: 1.71, 95% CI 1.19-2.46) and those living in mother-headed households (aOR: 2.39, 95% CI 1.43-3.99) were more likely to have a positive RDT. Living more than 5 km away from the nearest health facility (aOR: 1.60, 95% CI 1.04-2.44) and presence of two or more under-5-years children in the household (aOR: 1.44, 95% CI 1.01-2.07) were also associated with increased risk of infection. CONCLUSION: One-third of the children U2 who participated in this survey had malaria infection, thus PMC could be a promising strategy to reduce malaria burden in young children in Plateaux region. Reinforcement of outreach services and targeting the poorest households should be prioritized to reduce the inequity in malaria prevention in children exposed to the infection.

Regular Humoral and Cellular Immune Responses in Individuals with Chronic Myeloid Leukemia Who Received a Full Vaccination Schedule against COVID-19.

Individuals with chronic myeloid leukemia (CML) constitute a unique group within individuals with oncohematological disease (OHD). They receive treatment with tyrosine kinase inhibitors (TKIs) that present immunomodulatory properties, and they may eventually be candidates for treatment discontinuation under certain conditions despite the chronic nature of the disease. In addition, these individuals present a lower risk of infection than other immunocompromised patients. For this study, we recruited a cohort of 29 individuals with CML in deep molecular response who were on treatment with TKIs (n = 23) or were on treatment-free remission (TFR) (n = 6), and compared both humoral and cellular immune responses with 20 healthy donors after receiving the complete vaccination schedule against SARS-CoV-2. All participants were followed up for 17 months to record the development of COVID-19 due to breakthrough infections. All CML individuals developed an increased humoral response, with similar seroconversion rates and neutralizing titers to healthy donors, despite the presence of high levels of immature B cells. On the whole, the cellular immune response was also comparable to that of healthy donors, although the antibody dependent cytotoxic activity (ADCC) was significantly reduced. Similar rates of mild breakthrough infections were observed between groups, although the proportion was higher in the CML individuals on TFR, most likely due to the immunomodulatory effect of these drugs. In conclusion, as with the healthy donors, the vaccination did not impede breakthrough infections completely in individuals with CML, although it prevented the development of severe or critical illness in this special population of individuals with OHD.

Persistent Immunity against SARS-CoV-2 in Individuals with Oncohematological Diseases Who Underwent Autologous or Allogeneic Stem Cell Transplantation after Vaccination.

The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic-HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated.

Coverage of intermittent preventive treatment of malaria in infants after four years of implementation in Sierra Leone.

BACKGROUND: Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. METHODS: A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10-23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence-assessed with rapid diagnostic tests-were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. RESULTS: A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38-55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81-31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30-84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30-83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20-62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. CONCLUSION: In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.

Strong Humoral but Not Cellular Immune Responses against SARS-CoV-2 in Individuals with Oncohematological Disease Who Were Treated with Rituximab before Receiving a Vaccine Booster.

The humoral immune response developed after receiving the full vaccination schedule against COVID-19 is impaired in individuals who received anti-CD20 therapy 6-9 months before vaccination. However, there is little information about the cellular immune responses elicited in these individuals. In this study, we analyzed the humoral and cellular immune responses in 18 individuals with hematological disease who received the last dose of rituximab 13.8 months (IQR 9.4-19) before the booster dose. One month after receiving the booster dose, the seroconversion rate in the rituximab-treated cohort increased from 83.3% to 88.9% and titers of specific IgGs against SARS-CoV-2 increased 1.53-fold (p = 0.0098), while the levels of neutralizing antibodies increased 3.03-fold (p = 0.0381). However, the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) from rituximab-treated individuals remained unchanged, and both antibody-dependent cellular cytotoxicity (ADCC) and direct cellular cytotoxicity (CDD) were reduced 1.7-fold (p = 0.0047) and 2.0-fold (p = 0.0086), respectively, in comparison with healthy donors. Breakthrough infections rate was higher in our cohort of rituximab-treated individuals (33.33%), although most of the infected patients (83.4%) developed a mild form of COVID-19. In conclusion, our findings confirm a benefit in the humoral, but not in the cellular, immune response in rituximab-treated individuals after receiving a booster dose of an mRNA-based vaccine against COVID-19.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu

Minimally Invasive Tissue Sampling Findings in 12 Patients With Coronavirus Disease 2019.

BACKGROUND: Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. METHODS: From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. CONCLUSIONS: MITS is useful for evaluating COVID-19-related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.

Minimally Invasive Tissue Sampling: A Tool to Guide Efforts to Reduce AIDS-Related Mortality in Resource-Limited Settings.

BACKGROUND: Available information on the causes of death among people living with human immunodeficiency virus (PLHIV) in low- and middle-income countries (LMICs) remains scarce. We aimed to provide data on causes of death in PLHIV from two LMICs, Brazil and Mozambique, to assess the impact of clinical misdiagnosis on mortality rates and to evaluate the accuracy of minimally invasive tissue sampling (MITS) in determining the cause of death in PLHIV. METHODS: We performed coupled MITS and complete autopsy on 164 deceased PLHIV (18 children, 36 maternal deaths, and 110 adults). HIV antibody levels and HIV RNA viral loads were determined from postmortem serum samples. RESULTS: Tuberculosis (22.7%), toxoplasmosis (13.9%), bacterial infections (13.9%), and cryptococcosis (10.9%) were the leading causes of death in adults. In maternal deaths, tuberculosis (13.9%), bacterial infections (13.9%), cryptococcosis (11.1%), and cerebral malaria (8.3%) were the most frequent infections, whereas viral infections, particularly cytomegalovirus (38.9%), bacterial infections (27.8%), pneumocystosis (11.1%), and HIV-associated malignant neoplasms (11.1%) were the leading cause among children. Agreement between the MITS and the complete autopsy was 100% in children, 91% in adults, and 78% in maternal deaths. The MITS correctly identified the microorganism causing death in 89% of cases. CONCLUSIONS: Postmortem studies provide highly granular data on the causes of death in PLHIV. The inaccuracy of clinical diagnosis may play a significant role in the high mortality rates observed among PLHIV in LMICs. MITS might be helpful in monitoring the causes of death in PLHIV and in highlighting the gaps in the management of the infections.

High within-host diversity found from direct genotyping on post-mortem tuberculosis specimens in a high-burden setting.

OBJECTIVES: To characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants. METHODS: Genotypic analysis by Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeats (MIRU-VNTR) was performed directly on 70 biopsy specimens from two or more different tissues involving 28 tuberculosis cases diagnosed post-mortem in Mozambique, a country with a high tuberculosis burden. RESULTS: Genotypic data from isolates collected from two or more tissues were obtained for 23 of the 28 cases (82.1%), allowing the analysis of within-patient diversity. MIRU-VNTR analysis revealed clonal diversity in ten cases (35.7%). Five cases showed allelic differences in three or more loci, suggesting mixed infection with two different strains. In half of the cases showing within-host diversity, one of the specimens associated with clonal heterogeneity was brain tissue. CONCLUSIONS: Direct MTB genotyping from post-mortem tissue samples revealed a frequent within-host Mycobacterium tuberculosis diversity, including mixed and polyclonal infections. Most of this diversity would have been overlooked if only standard analysis of respiratory specimens had been performed.

Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings.

Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases.

Zika virus infection in pregnant travellers and impact on childhood neurodevelopment in the first two years of life: A prospective observational study.

BACKGROUND: The emergence of Zika virus (ZIKV) represents a threat with consequences on maternal and children's health. We aimed to assess the clinical and epidemiological characteristics of pregnant women returning from ZIKV affected areas, and the effects of maternal ZIKV infection on birth outcomes and children's health. METHODS: This was a hospital-based prospective observational study conducted at the Hospital Clínic of Barcelona and Hospital Sant Joan de Déu, Barcelona, Spain, from January 2016 to February 2020. RESULTS: One hundred and ninety-five pregnant women who had travelled to ZIKV affected areas during pregnancy were recruited. Four women (2.1%) had a confirmed ZIKV infection, 40 women (20.5%) a probable infection, and 151 (77.4%) were negative for ZIKV. Among the ZIKV confirmed cases, a pregnant woman suffered a miscarriage, highly plausible to be associated with ZIKV infection. Brain cysts and microcalcifications were detected in 7% of fetuses or infants from women with confirmed or probable ZIKV infection. Neurodevelopmental delay in the language function was found in 33.3% out of the 21 children evaluated. CONCLUSIONS: These findings contribute to the understanding of ZIKV prevalence estimates, and the impact of maternal ZIKV infection on pregnancy outcomes and children's health. Results highlight the importance of long-term surveillance in pregnant travellers and their children.

Conceptual frameworks for understanding the acceptability and feasibility of the minimally invasive autopsy to determine cause of death: Findings from the CADMIA Study in western Kenya.

Establishing the cause of death (CoD) is critical to better understanding health and prioritizing health investments, however the use of full post-mortem examination is rare in most low and middle-income counties for multiple reasons. The use of minimally invasive autopsy (MIA) approaches, such as needle biopsies, presents an alternate means to assess CoD. In order to understand the feasibility and acceptability of MIA among communities in western Kenya, we conducted focus groups and in-depth interviews with next-of-kin of recently deceased persons, community leaders and health care workers in Siaya and Kisumu counties. Results suggest two conceptual framework can be drawn, one with facilitating factors for acceptance of MIA due to the ability to satisfy immediate needs related to interest in learning CoD or protecting social status and honoring the deceased), and one framework covering barriers to acceptance of MIA, for reasons relating to the failure to serve an existing need, and/or the exacerbation of an already difficult time.

Lay knowledge of cervical cancer in Manhiça district, Mozambique: a qualitative study.

BACKGROUND: Mozambique has one of the highest cervical cancer incidence rates in the world. Health interventions are still being conceived solely from a non-communicable disease standpoint despite that it is also a sexual and reproductive health problem. The objective of this study was to assess the extent to which lay perceptions of cervical cancer align with biomedical knowledge from the standpoint of sexual and reproductive health. METHODS: 10 focus group discussions were carried out with 10 target groups in Manhiça. The target groups were diverse in terms of age, sex, educational level and occupation. There were a total of 116 participants. The focus groups discussions were applied to obtain verbal information and trigger debates around beliefs and attitudes about cervical cancer as well as to explore notions of transmission and aetiology of the disease. The discussions were recorded for later transcription and analysis, following a combination of content and thematic analysis. RESULTS: Participants were familiar with the biomedical term 'cervical cancer' but knowledge of its aetiology and transmission was limited. Cervical cancer was readily associated to sexual transmission and sexually transmitted infections, and conceived as a 'wound that does not heal'. The term 'cancer' caused confusion, as it was perceived to happen only in limbs, understood as hereditary, not transmissible and as an illness of the West. CONCLUSIONS: Lay perceptions of cervical cancer do, to a large extent, align with biomedical ones, thus, there is common ground to frame future health interventions from a sexual and reproductive health standpoint. Some misperceptions were identified which could be reduced through social behaviour change communication initiatives.

Hydroxychloroquine efficacy and safety in preventing SARS-CoV-2 infection and COVID-19 disease severity during pregnancy (COVID-Preg): a structured summary of a study protocol for a randomised placebo controlled trial.

OBJECTIVES: The primary objectives of the study are: 1. To assess the effect of hydroxychloroquine (HCQ) in reducing SARS-CoV-2 viral shedding by PCR in infected pregnant women with mild symptoms. 2. To assess the efficacy of HCQ to prevent SARS-CoV-2 infection in pregnant women in contact with an infected or suspected case. 3. To evaluate the effect of HCQ in preventing the development of the COVID-19 disease in asymptomatic SARS-CoV-2-infected pregnant women. The secondary objectives are: 1. To determine the effect of HCQ on the clinical course and duration of the COVID-19 disease in SARS-CoV-2-infected pregnant women. 2. To determine the impact of HCQ on the risk of hospitalization and mortality of SARS-CoV-2-infected pregnant women. 3. To assess the safety and tolerability of HCQ in pregnant women. 4. To describe the clinical presentation of SARS-CoV-2 infection during pregnancy. 5. To describe the effects of maternal SARS-CoV-2 infection on pregnancy and perinatal outcomes by treatment group. 6. To determine the risk of vertical transmission (intra-utero and intra-partum) of SARS-CoV-2. TRIAL DESIGN: Randomized double-blind placebo-controlled two-arm multicentre clinical trial to evaluate the safety and efficacy of HCQ to prevent and/or minimize SARS-CoV-2 infection during pregnancy. Participants will be randomized to receive a 14-day oral treatment course of HCQ or placebo, ratio 1:1. PARTICIPANTS: Study population: pregnant women undergoing routine prenatal follow up or attending emergency units at the participating hospitals who report either symptoms/signs suggestive of COVID-19 disease or close contact with a suspected or confirmed COVID-19 case. Inclusion criteria Women will be invited to participate in the trial and sign an informed consent if they meet the following inclusion criteria. • Presenting with fever (≥37.5°C) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, dysgeusia, headache) OR being contact* of a SARS-CoV-2 confirmed or suspected case in the past 14 days • More than 12 weeks of gestation (dated by ultrasonography) • Agreement to deliver in the study hospitals Exclusion criteria • Known hypersensitivity to HCQ or other 4-amonoquinoline compounds • History of retinopathy of any aetiology • Concomitant use of digoxin, cyclosporine, cimetidine • Known liver disease • Clinical history of cardiac pathology including known long QT syndrome • Unable to cooperate with the requirements of the study • Participating in other intervention studies • Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours) The study participants will be stratified by clinical presentation and SARS-CoV-2 PCR results. Assignment of participants to study groups will be as follows: • SARS-CoV-2-PCR confirmed, infected pregnant women: a. symptomatic (n=100) b. asymptomatic (n=100) • SARS-CoV-2 PCR negative pregnant women in contact* with a SARS-CoV-2-infected confirmed or suspected case (n=514). *The ECDC definition of close contact will be followed. The trial will be conducted in five hospitals in Spain: Hospital Clínic of Barcelona, Hospital Sant Joan de Déu and Hospital de la Santa Creu i Sant Pau, in Barcelona, and HM Puerta del Sur and Hospital Universitario de Torrejón, in Madrid. INTERVENTION AND COMPARATOR: Participants will be randomized to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days) or placebo (2 tablets for three days, followed by one tablet for 11 days). MAIN OUTCOMES: The primary outcome is the number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start (one week after treatment is completed). RANDOMISATION: Allocation of participants to study arms will be done centrally by the trial's Sponsor (the Barcelona Institute for Global Health, ISGlobal) by block randomization. This method will ensure balanced allocation to both arms. The electronic CRF will automatically assign a study number to each participant, depending on her study group and recruitment site. Each number will be related to a treatment number, which assigns them to one of the study arms. BLINDING (MASKING): Participants, caregivers, investigators and those assessing the outcomes will be blinded to group assignment. Study tablets (HCQ and placebo) will be identically packaged in small opaque bottles. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study requires 200 SARS-CoV-2 infected and 514 contact pregnant women, randomised 1:1 with 100 and 227 respectively in each study arm. TRIAL STATUS: Protocol version 1.0, from May 8th, 2020. Recruitment is ongoing (first patient recruited the 19th May 2020 and recruitment end anticipated by December 2020). TRIAL REGISTRATION: EudraCT number: 2020-001587-29, registered 2 April 2020. Clinicaltrials.gov identifier: NCT04410562 , retrospectively registered 1 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

The duration of chemoprophylaxis against malaria after treatment with artesunate-amodiaquine and artemether-lumefantrine and the effects of pfmdr1 86Y and pfcrt 76T: a meta-analysis of individual patient data.

BACKGROUND: The majority of Plasmodium falciparum malaria cases in Africa are treated with the artemisinin combination therapies artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), with amodiaquine being also widely used as part of seasonal malaria chemoprevention programs combined with sulfadoxine-pyrimethamine. While artemisinin derivatives have a short half-life, lumefantrine and amodiaquine may give rise to differing durations of post-treatment prophylaxis, an important additional benefit to patients in higher transmission areas. METHODS: We analyzed individual patient data from 8 clinical trials of AL versus AS-AQ in 12 sites in Africa (n = 4214 individuals). The time to PCR-confirmed reinfection after treatment was used to estimate the duration of post-treatment protection, accounting for variation in transmission intensity between settings using hidden semi-Markov models. Accelerated failure-time models were used to identify potential effects of covariates on the time to reinfection. The estimated duration of chemoprophylaxis was then used in a mathematical model of malaria transmission to determine the potential public health impact of each drug when used for first-line treatment. RESULTS: We estimated a mean duration of post-treatment protection of 13.0 days (95% CI 10.7-15.7) for AL and 15.2 days (95% CI 12.8-18.4) for AS-AQ overall. However, the duration varied significantly between trial sites, from 8.7-18.6 days for AL and 10.2-18.7 days for AS-AQ. Significant predictors of time to reinfection in multivariable models were transmission intensity, age, drug, and parasite genotype. Where wild type pfmdr1 and pfcrt parasite genotypes predominated (<=20% 86Y and 76T mutants, respectively), AS-AQ provided ~ 2-fold longer protection than AL. Conversely, at a higher prevalence of 86Y and 76T mutant parasites (> 80%), AL provided up to 1.5-fold longer protection than AS-AQ. Our simulations found that these differences in the duration of protection could alter population-level clinical incidence of malaria by up to 14% in under-5-year-old children when the drugs were used as first-line treatments in areas with high, seasonal transmission. CONCLUSION: Choosing a first-line treatment which provides optimal post-treatment prophylaxis given the local prevalence of resistance-associated markers could make a significant contribution to reducing malaria morbidity.

Blood cytokine, chemokine and growth factor profiling in a cohort of pregnant women from tropical countries.

The immune status of women changes during and after pregnancy, differs between blood compartments at delivery and is affected by environmental factors particularly in tropical areas endemic for multiple infections. We quantified the plasma concentration of a set of thirty-one TH1, TH2, TH17 and regulatory cytokines, pro-inflammatory and anti-inflammatory cytokines and chemokines, and growth factors (altogether biomarkers), in a cohort of 540 pregnant women from five malaria-endemic tropical countries. Samples were collected at recruitment (first antenatal visit), delivery (periphery, cord and placenta) and postpartum, allowing a longitudinal analysis. We found the lowest concentration of biomarkers at recruitment and the highest at postpartum, with few exceptions. Among them, IL-6, HGF and TGF-ß had the highest levels at delivery, and even higher concentrations in the placenta compared to peripheral blood. Placental concentrations were generally higher than peripheral, except for eotaxin that was lower. We also compared plasma biomarker concentrations between the tropical cohort and a control group from Spain at delivery, presenting overall higher biomarker levels the tropical cohort, particularly pro-inflammatory cytokines and growth factors. Only IL-6 presented lower levels in the tropical group. Moreover, a principal component analysis of biomarker concentrations at delivery showed that women from Spain grouped more homogenously, and that IL-6 and IL-8 clustered together in the tropical cohort but not in the Spanish one. Plasma cytokine concentrations correlated with Plasmodium antibody levels at postpartum but not during pregnancy. This basal profiling of immune mediators over gestation and in different compartments at delivery is important to subsequently understand response to infections and clinical outcomes in mothers and infants in tropical areas.

Costs associated with delivering HPV vaccination in the context of the first year demonstration programme in southern Mozambique.

BACKGROUND: In Mozambique cervical cancer is a public health threat, due to its high incidence and limited access to early diagnosis of precancerous lesions. International organisations are supporting the introduction of human papillomavirus (HPV) vaccines in low- and middle-income countries. Some of these countries recently conducted demonstration programmes, which included evaluation of acceptability, coverage, and practicality of implementation and of integration in existing programmes. Information on costs of delivering the vaccine is needed to overcome the challenges of reaching vaccine potential recipients in rural and remote areas. METHODS: We estimated the financial and economic costs of delivering HPV vaccination to ten-year-old girls at schools for the first vaccination cycle of the demonstration programme in the Manhiça district (southern Mozambique), delivered throughout 2014. We also estimated costs of an alternative scenario with a reduced number of doses and personnel, which was analogous to the second vaccination cycle delivered throughout 2015. Cost estimates followed a micro-costing approach and included interviews with key informants at different administrative levels through the administration of standard questionnaires developed by the World Health Organisation. RESULTS: Considering only data from the first vaccination cycle (2014), which consisted in the administration of three doses, the average economic cost was US$17.59 per dose and US$52.29 per fully-immunised girl (FIG). Financial cost per dose (US$6.07) and per FIG (US$17.95) were substantially lower. The economic cost was US$15.53 per dose and US$31.14 per FIG when estimating an alternative cost scenario with reduced number of doses and personnel. CONCLUSIONS: The average economic cost per dose was lower than the ones recently reported for low- and middle-income countries. However, our estimation of the financial cost per FIG was higher than the ones observed elsewhere (ranging from US$2.49 in India to US$20.36 in Vietnam) due to the high percentage of out-of-school girls which, reduced vaccine coverage and, therefore, reduced the denominator. Due to budget constraints, if Mozambique is to implement nation-wide HPV vaccination targeted to ten-year-old girls at schools, a reduction in personnel costs should be operated either by restricting the outreach vaccinator team or the number of supervision visits.

Predictors of personal exposure to black carbon among women in southern semi-rural Mozambique.

Sub-Saharan Africa (SSA) has the highest proportion of people using unclean fuels for household energy, which can result in products of incomplete combustion that are damaging for health. Black carbon (BC) is a useful marker of inefficient combustion-related particles; however, ambient air quality data and temporal patterns of personal exposure to BC in SSA are scarce. We measured ambient elemental carbon (EC), comparable to BC, and personal exposure to BC in women of childbearing age from a semi-rural area of southern Mozambique. We measured ambient EC over one year (2014-2015) using a high-volume sampler and an off-line thermo-optical-transmission method. We simultaneously measured 5-min resolved 24-h personal BC using a portable MicroAeth (AE51) in 202 women. We used backwards stepwise linear regression to identify predictors of log-transformed 24-h mean and peak (90th percentile) personal BC exposure. We analyzed data from 187 non-smoking women aged 16-46 years. While daily mean ambient EC reached moderate levels (0.9 µg/m3, Standard Deviation, SD: 0.6 µg/m3), daily mean personal BC reached high levels (15 µg/m3, SD: 19 µg/m3). Daily patterns of personal exposure revealed a peak between 6 and 7 pm (>35 µg/m3), attributable to kerosene-based lighting. Key determinants of mean and peak personal exposure to BC were lighting source, kitchen type, ambient EC levels, and temperature. This study highlights the important contribution of lighting sources to personal exposure to combustion particles in populations that lack access to clean household energy.

Socio-anthropological methods to study the feasibility and acceptability of the minimally invasive autopsy from the perspective of local communities: lessons learnt from a large multi-centre study.

The minimally invasive autopsy (MIA), an innovative approach for obtaining post-mortem samples of key organs, is increasingly being recognized as a robust methodology for cause of death (CoD) investigation, albeit so far limited to pilot studies and research projects. A better understanding of the real causes of death in middle- and low-income countries, where underlying causes of death are seldom determined, would allow improved health planning, more targeted prioritization of available resources and the implementation of coherent public health policies. This paper discusses lessons learnt from the implementation of a Feasibility and Acceptability (F&A) study evaluating the MIA approach in five countries: Gabon, Kenya, Mali, Mozambique and Pakistan. This article reports the methodological choices made to document sociocultural and religious norms around death, to examine community and relatives' attitudes and perceptions towards MIA, and to identify factors motivating the MIA's acceptance and refusal. We used ethnography, grounded theory and framework method approaches. In-depth and semi-structured interviews and focus group discussions with key informants, including next of kin of deceased individuals and healthcare providers, were conducted. Participant observation and direct observation of procedures and ceremonies around death were organized in all study sites. In Mozambique, MIA procedures were observed and case studies conducted. The implementation of this F&A protocol has provided critical lessons that could facilitate the future implementation of post-mortem procedures for CoD investigation. These include the need for early community engagement, staff training and preparedness, flexibility to adapt the protocol, gathering qualitative data from diverse sources, and triangulation of the data. We have applied a rigorous, effective and culturally sensitive methodological approach to assess the F&A of MIA in resource-constrained settings. We strongly recommend that such an approach is applied in settings where MIAs or similar post-mortem sensitive procedures are to be introduced.

Weak surveillance and policy attention to cancer in global health: the example of Mozambique.

Cancer is an emerging public health problem in sub-Saharan Africa due to population growth, ageing and westernisation of lifestyles. The increasing burden of cancer calls for urgent policy attention to develop cancer prevention and control programmes. Cancer surveillance is an essential prerequisite. Only one in five low-income and middle-income countries have the necessary data to drive policy and reduce the cancer burden. In this piece, we use data from Mozambique over a 50-year period to illustrate cancer epidemiological trends in low-income and middle-income countries to hypothesise potential circumstances and factors that could explain changes in cancer burden and to discuss surveillance weaknesses and potential improvements. Like many low-income and middle-income countries, Mozambique faces the dual challenge of a still high morbidity and mortality due to infectious diseases in rural areas and increased incidence of cancers associated with westernisation of lifestyles in urban areas, as well as a rise of cancers related to the HIV epidemic. An increase in cancer burden and changes in the cancer profile should be expected in coming years. The Mozambican healthcare and health-information systems, like in many other low-income and middle-income countries, are not prepared to face this epidemiological transition, which deserves increasing policy attention.