RTS,S/AS02A Malaria Vaccine-Induced IgG Responses Equally Recognize Native-Like Fucosylated and Nonfucosylated Plasmodium falciparum Circumsporozoite Proteins.

The RTS,S/AS02A malaria vaccine is based on the Plasmodium falciparum circumsporozoite protein (PfCSP), which is O-fucosylated on the sporozoite surface. We determined whether RTS,S/AS02A-induced immunoglobulin G (IgG) antibodies recognize vaccine-like nonfucosylated PfCSP better than native-like fucosylated PfCSP. Similar to previous vaccine trials, RTS,S/AS02A vaccination induced high anti-PfCSP IgG levels associated with malaria protection. IgG recognition of nonfucosylated and fucosylated PfCSP was equivalent, suggesting that PfCSP fucosylation does not affect antibody recognition. Clinical Trials Registration. NCT00197041.

Molecular detection of Helicobacter pylori and its genotypic antimicrobial resistance patterns in dyspeptic Mozambican patients.

BACKGROUND: Helicobacter pylori strains show a high level of genotypic diversity and express several genes that contribute to their pathogenicity and resistance. In Mozambique, there is lack of information regarding its resistance pattern to antibiotics. In this study, we aimed to investigate the prevalence of H. pylori and its genotypic resistance to clarithromycin, metronidazole, and fluoroquinolones in Mozambican dyspeptic patients. Since appropriate eradication should be based on the local resistance rate, our data will guide clinicians in choosing the best drugs for the effective treatment of H. pylori-infected patients. METHODS: This is a cross-sectional descriptive study conducted between June 2017 and June 2020, in which 171 dyspeptic patients were recruited, and through upper gastrointestinal endoscopy, gastric biopsies were collected from those patients. Polymerase chain reaction was performed for the detection of H. pylori and its resistance mechanisms to clarithromycin (23S rRNA), metronidazole (rdxA), and fluoroquinolones (gyrA); mutations conferring resistance to these antibiotics were investigated by sequencing 23S rRNA, rdxA, and gyrA genes. RESULTS: Of the 171 samples tested, H. pylori was detected in 56.1% (96/171). The clarithromycin resistance rate was 10.4% (the responsible mutations were A2142G and A2143G), the metronidazole resistance rate was 55.2% (4 types of mutations responsible for metronidazole resistance were identified which include, D59N, R90K, H97T, and A118T. However, in many cases, they appeared in combination, with D59N + R90K + A118T being the most frequent combination), and the fluoroquinolones resistance rate was 20% (the responsible mutations were N87I and D91G). CONCLUSION: H. pylori infection remains common in dyspeptic Mozambican patients. High resistance to metronidazole and fluoroquinolones requires continuous monitoring of antibiotic resistance and adaptation of therapy to eradicate this infection.

Communication strategies used by medical physicians when delivering bad news at the Maputo Central Hospital, Mozambique: a cross-sectional study.

BACKGROUND: Physicians' communication with patients and their families is important during both the disease diagnosis and prognosis stages and through the follow-up process. Effective physician communication improves patients' quality of life and satisfaction with care and helps reduce suffering for those newly diagnosed with advanced progressive illnesses. This study aims to identify the communication strategies physicians use in the transition to palliative care and how these professionals perceive their academic and clinical preparation concerning this task. METHODS: A cross-sectional and quantitative study. Physicians providing palliative care at the Maputo Central Hospital, Mozambique, were invited to complete a 17-question questionnaire. This questionnaire was based on a Brazilian adaptation of the Setting-Perception-Invitation-Knowledge-Emotions-Strategy (SPIKES) tool, the P-A-C-I-E-N-T-E protocol, with additional questions regarding socio-demographic details and the integration of "communication of bad news" into hospital training. RESULTS: Of the 121 participants, 62 (51.2%) were male, and 110 (90.9%) were general practitioners, with a median age of 36 years old. They had worked in clinical practice for a median of 8 years and in their current department for three years. The majority of the participants considered that they have an acceptable or good level of bad news communication skills and believed that they do it in a clear and empathic way, paying attention to the patient's requests and doubts; however, most were not aware of the existing tools to assist them in this task and suggested that delivering bad news ought to be integrated into the undergraduate medical course and included in hospital training. CONCLUSIONS: This study adds to our understanding of physicians' strategies when communicating bad news in the context of palliative care at one Mozambique hospital. As palliative care is not fully implemented in Mozambique, it is important to use protocols suitable to the country's healthcare level to improve how doctors deal with patients and their family members.

Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children.

BACKGROUND: RTS,S is the first malaria vaccine recommended for implementation among young children at risk. However, vaccine efficacy is modest and short-lived. Antibodies play the major role in vaccine-induced immunity, but knowledge on the induction, decay, and determinants of antibody function is limited, especially among children. Antibodies that promote opsonic phagocytosis and other cellular functions appear to be important contributors to RTS,S immunity. METHODS: We studied a phase IIb trial of RTS,S/AS02 conducted in young children in malaria-endemic regions of Mozambique. We evaluated the induction of antibodies targeting the circumsporozoite protein (CSP, vaccine antigen) that interact with Fcγ-receptors (FcRγs) and promote phagocytosis (neutrophils, monocytes, THP-1 cells), antibody-dependent respiratory burst (ADRB) by neutrophils, and natural killer (NK) cell activity, as well as the temporal kinetics of responses over 5 years of follow-up (ClinicalTrials.gov registry number NCT00197041). RESULTS: RTS,S vaccination induced CSP-specific IgG with FcγRIIa and FcγRIII binding activity and promoted phagocytosis by neutrophils, THP-1 monocytes, and primary human monocytes, neutrophil ADRB activity, and NK cell activation. Responses were highly heterogenous among children, and the magnitude of neutrophil phagocytosis by antibodies was relatively modest, which may reflect modest vaccine efficacy. Induction of functional antibodies was lower among children with higher malaria exposure. Functional antibody magnitude and the functional activity of antibodies largely declined within a year post-vaccination, and decay were highest in the first 6 months, consistent with the decline in vaccine efficacy over that time. Decay rates varied for different antibody parameters and decay was slower for neutrophil phagocytosis. Biostatistical modelling suggested IgG1 and IgG3 contribute in promoting FcγR binding and phagocytosis, and IgG targeting the NANP-repeat and C-terminal regions CSP were similarly important for functional activities. CONCLUSIONS: Results provide new insights to understand the modest and time-limited efficacy of RTS,S in children and the induction of antibody functional activities. Improving the induction and maintenance of antibodies that promote phagocytosis and cellular functions, and combating the negative effect of malaria exposure on vaccine responses are potential strategies for improving RTS,S efficacy and longevity.

Clinical and epidemiological aspects of SARS-CoV-2 infection among pregnant and postpartum women in Mozambique: a prospective cohort study.

BACKGROUND: Although there is a significant increase of evidence regarding the prevalence and impact of COVID-19 on maternal and perinatal outcomes, data on the effects of the pandemic on the obstetric population in sub-Saharan African countries are still scarce. Therefore, the study aims were to assess the prevalence and impact of COVID-19 on maternal and neonatal outcomes in the obstetric population at Central Hospital of Maputo (HCM), Mozambique. METHODS: Prospective cohort study conducted at teaching and referral maternity, HCM, from 20 October 2020 to 22 July 2021. We collected maternal and perinatal outcomes up to 6 weeks postpartum of eligible women (pregnant and postpartum women-up to the 14th day postpartum) screened for COVID-19 (individual test for symptomatic participants and pool testing for asymptomatic). The primary outcome was maternal death, Severe Acute Respiratory Syndrome (SARS) and Intensive Care Unit (ICU) admission. We estimated the COVID-19 prevalence and the unadjusted RR (95% CI) for maternal and perinatal outcomes. We used the chi-square or Fisher's exact test to compare categorical variables (two-sided p-value < 0.05 for statistical significance). RESULTS: We included 239 participants. The overall prevalence of COVID-19 was 9.2% (22/239) and in the symptomatic group was 32.4% (11/34). About 50% of the participants with COVID-19 were symptomatic. Moreover, the most frequent symptoms were dyspnoea (33.3%), cough (28.6%), anosmia (23.8%), and fever (19%). Not having a partner, being pregnant, and alcohol consumption were vulnerability factors for SARS-CoV-2 infection. The risk of adverse maternal and neonatal outcomes (abortion, foetal death, preterm birth, Apgar, and NICU admission) was not significantly increased with COVID-19. Moreover, we did not observe a significant difference in the primary outcomes (SARS, ICU admission and maternal death) between COVID-19 positive and COVID-19 negative groups. CONCLUSION: The prevalence of COVID-19 in the obstetric population is higher than in the general population, and fifty percent of pregnant and postpartum women with COVID-19 infection are asymptomatic. Not having a partner and alcohol consumption were factors of greatest vulnerability to SARS-COV-2 infection. Moreover, being pregnant versus postpartum was associated with increased vulnerability to COVID-19. Data suggest that pregnant women with COVID-19 may have a higher frequency of  COVID-19 infection, reinforcing the need for universal testing, adequate follow-up for this population, and increasing COVID-19 therapy facilities in Mozambique. Moreover, provide counselling during Antenatal care for COVID-19 preventive measures. However, more prospective and robust studies are needed to assess these findings.

Altered Mental Status Among Febrile Hospitalized HIV-Infected Children Aged 0-59 Months in Mozambique.

BACKGROUND: Altered mental status (AMS) is a priority presenting sign that must be assessed in HIV-infected, febrile children, yet diagnosis is difficult in areas with limited diagnostic capacity. Malaria and bacterial meningitis have been reported as the most common causes of AMS in febrile children presenting to the hospital in sub-Saharan Africa. However, in an HIV-infected child, central nervous system manifestations are diverse. METHODS: We conducted a clinical observational study of HIV-infected febrile children, aged 0-59 months, hospitalized in Mozambique and prospectively followed. Within this cohort, a nested study was designed to characterize children admitted with AMS and to assess factors associated with mortality. Univariate and multivariable analysis were performed comparing characteristics of the cohort by AMS status and evaluated demographic and clinical factors by in-hospital mortality outcome. RESULTS: In total, 727 children were enrolled between April 2016 and February 2019, 16% had AMS at admission. HIV-infected, febrile children, who presented with AMS and who had a diagnosis of bacteremia, had a 4-fold increased relative odds of in-hospital mortality, and children who presented with neurologic symptoms on admission had a roughly 8-fold higher odds of in-hospital mortality relative to children without presenting neurologic findings. CONCLUSIONS: Mozambique has a pressing need to expand local diagnostic capacity. Our results highlight the critical need for clinicians to incorporate a broader differential into their potential causes of AMS, and to develop a Ministry of Health approved diagnostic and management algorithm, which is standardly used, to manage patients for whom reliable and relevant diagnostic services are not available.

Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure.

BACKGROUND: Leading malaria vaccine, RTS,S, is based on the circumsporozoite protein (CSP) of sporozoites. RTS,S confers partial protection against malaria in children, but efficacy wanes relatively quickly after primary immunization. Vaccine efficacy has some association with anti-CSP IgG; however, it is unclear how these antibodies function, and how functional antibodies are induced and maintained over time. Recent studies identified antibody-complement interactions as a potentially important immune mechanism against sporozoites. Here, we investigated whether RTS,S vaccine-induced antibodies could function by interacting with complement. METHODS: Serum samples were selected from children in a phase IIb trial of RTS,S/AS02A conducted at two study sites of high and low malaria transmission intensity in Manhiça, Mozambique. Samples following primary immunization and 5-year post-immunization follow-up time points were included. Vaccine-induced antibodies were characterized by isotype, subclass, and epitope specificity, and tested for the ability to fix and activate complement. We additionally developed statistical methods to model the decay and determinants of functional antibodies after vaccination. RESULTS: RTS,S vaccination induced anti-CSP antibodies that were mostly IgG1, with some IgG3, IgG2, and IgM. Complement-fixing antibodies were effectively induced by vaccination, and targeted the central repeat and C-terminal regions of CSP. Higher levels of complement-fixing antibodies were associated with IgG that equally recognized both the central repeat and C-terminal regions of CSP. Older age and higher malaria exposure were significantly associated with a poorer induction of functional antibodies. There was a marked decay in functional complement-fixing antibodies within months after vaccination, as well as decays in IgG subclasses and IgM. Statistical modeling suggested the decay in complement-fixing antibodies was mostly attributed to the waning of anti-CSP IgG1, and to a lesser extent IgG3. CONCLUSIONS: We demonstrate for the first time that RTS,S can induce complement-fixing antibodies in young malaria-exposed children. The short-lived nature of functional responses mirrors the declining vaccine efficacy of RTS,S over time. The negative influence of age and malaria exposure on functional antibodies has implications for understanding vaccine efficacy in different settings. These findings provide insights into the mechanisms and longevity of vaccine-induced immunity that will help inform the future development of highly efficacious and long-lasting malaria vaccines.

Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children.

BACKGROUND: The RTS,S/AS01E vaccine provides partial protection against malaria in African children, but immune responses have only been partially characterized and do not reliably predict protective efficacy. We aimed to evaluate comprehensively the immunogenicity of the vaccine at peak response, the factors affecting it, and the antibodies associated with protection against clinical malaria in young African children participating in the multicenter phase 3 trial for licensure. METHODS: We measured total IgM, IgG, and IgG1-4 subclass antibodies to three constructs of the Plasmodium falciparum circumsporozoite protein (CSP) and hepatitis B surface antigen (HBsAg) that are part of the RTS,S vaccine, by quantitative suspension array technology. Plasma and serum samples were analyzed in 195 infants and children from two sites in Ghana (Kintampo) and Mozambique (Manhiça) with different transmission intensities using a case-control study design. We applied regression models and machine learning techniques to analyze immunogenicity, correlates of protection, and factors affecting them. RESULTS: RTS,S/AS01E induced IgM and IgG, predominantly IgG1 and IgG3, but also IgG2 and IgG4, subclass responses. Age, site, previous malaria episodes, and baseline characteristics including antibodies to CSP and other antigens reflecting malaria exposure and maternal IgGs, nutritional status, and hemoglobin concentration, significantly affected vaccine immunogenicity. We identified distinct signatures of malaria protection and risk in RTS,S/AS01E but not in comparator vaccinees. IgG2 and IgG4 responses to RTS,S antigens post-vaccination, and anti-CSP and anti-P. falciparum antibody levels pre-vaccination, were associated with malaria risk over 1-year follow-up. In contrast, antibody responses to HBsAg (all isotypes, subclasses, and timepoints) and post-vaccination IgG1 and IgG3 to CSP C-terminus and NANP were associated with protection. Age and site affected the relative contribution of responses in the correlates identified. CONCLUSIONS: Cytophilic IgG responses to the C-terminal and NANP repeat regions of CSP and anti-HBsAg antibodies induced by RTS,S/AS01E vaccination were associated with malaria protection. In contrast, higher malaria exposure at baseline and non-cytophilic IgG responses to CSP were associated with disease risk. Data provide new correlates of vaccine success and failure in African children and reveal key insights into the mode of action that can guide development of more efficacious next-generation vaccines.

Research ethics review at University Eduardo Mondlane (UEM)/Maputo Central Hospital, Mozambique (2013-2016): a descriptive analysis of the start-up of a new research ethics committee (REC).

BACKGROUND: Mozambique has seen remarkable growth in biomedical research over the last decade. To meet a growing need, the National Committee for Bioethics in Health of Mozambique (CNBS) encouraged the development of ethical review processes at institutions that regularly conduct medical and social science research. In 2012, the Faculty of Medicine (FM) of University Eduardo Mondlane (UEM) and the Maputo Central Hospital (MCH) established a joint Institutional Committee on Bioethics for Health (CIBS FM & MCH). This study examines the experience of the first 4 years of the CIBS FM & MCH. METHODS: This study provides a descriptive, retrospective analysis of research protocols submitted to and approved by the CIBS FM & MCH between March 1, 2013 and December 31, 2016, together with an analysis of the Committee's respective reviews and actions. RESULTS: A total of 356 protocols were submitted for review during the period under analysis, with 309 protocols approved. Sixty-four percent were submitted by students, faculty, and researchers from UEM, mainly related to Master's degree research (42%). Descriptive cross-sectional studies were the most frequently reviewed research (61%). The majority were prospective (71%) and used quantitative methodologies (51%). The Departments of Internal Medicine at MCH and Community Health at the FM submitted the most protocols from their respective institutions, with 38 and 53% respectively. The CIBS's average time to final approval for all protocols was 56 days, rising to 161 for the 40 protocols that required subsequent national-level review by the CNBS. CONCLUSIONS: Our results show that over its first 4 years, the CIBS FM & MCH has been successful in managing a constant demand for protocol review and that several broad quality improvement initiatives, such as investigator mentoring and an electronic protocol submission platform have improved efficiency in the review process and the overall quality of the protocols submitted. Beyond Maputo, long-term investments in training and ethical capacity building for CIBS across the country continue to be needed, as Mozambique develops greater capacity for research and makes progress toward improving the health of all its citizens.

Distinct Helper T Cell Type 1 and 2 Responses Associated With Malaria Protection and Risk in RTS,S/AS01E Vaccinees.

BACKGROUND: The RTS,S/AS01E malaria vaccine has moderate efficacy, lower in infants than children. Current efforts to enhance RTS,S/AS01E efficacy would benefit from learning about the vaccine-induced immunity and identifying correlates of malaria protection, which could, for instance, inform the choice of adjuvants. Here, we sought cellular immunity-based correlates of malaria protection and risk associated with RTS,S/AS01E vaccination. METHODS: We performed a matched case-control study nested within the multicenter African RTS,S/AS01E phase 3 trial. Children and infant samples from 57 clinical malaria cases (32 RTS,S/25 comparator vaccinees) and 152 controls without malaria (106 RTS,S/46 comparator vaccinees) were analyzed. We measured 30 markers by Luminex following RTS,S/AS01E antigen stimulation of cells 1 month postimmunization. Crude concentrations and ratios of antigen to background control were analyzed. RESULTS: Interleukin (IL) 2 and IL-5 ratios were associated with RTS,S/AS01E vaccination (adjusted P ≤ .01). IL-5 circumsporozoite protein (CSP) ratios, a helper T cell type 2 cytokine, correlated with higher odds of malaria in RTS,S/AS01E vaccinees (odds ratio, 1.17 per 10% increases of CSP ratios; P value adjusted for multiple testing = .03). In multimarker analysis, the helper T cell type 1 (TH1)-related markers interferon-γ, IL-15, and granulocyte-macrophage colony-stimulating factor protected from subsequent malaria, in contrast to IL-5 and RANTES, which increased the odds of malaria. CONCLUSIONS: RTS,S/AS01E-induced IL-5 may be a surrogate of lack of protection, whereas TH1-related responses may be involved in protective mechanisms. Efforts to develop second-generation vaccine candidates may concentrate on adjuvants that modulate the immune system to support enhanced TH1 responses and decreased IL-5 responses.

Assessment of coverage of preventive treatment and insecticide-treated mosquito nets in pregnant women attending antenatal care services in 11 districts in Mozambique in 2011: the critical role of supply chain.

BACKGROUND: Malaria during pregnancy is associated with poor maternal and pregnancy outcome and the World Health Organization recommends the administration of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) and distribution of insecticide-treated mosquito nets (ITNs) to all pregnant women attending antenatal care (ANC) services. This study was conducted with the aim to assess the uptake of IPTp and ITNs in pregnant women attending ANC services and correlate with ANC attendance and frequency of stock-outs in 22 health facilities Mozambique. METHODS: A cross-sectional study was conducted between July and December 2011 in 22 health units in 11 districts situated in 11 provinces in Mozambique. Two health facilities were selected per district (one urban and one rural). Data were collected by reviewing logbooks of antenatal consultations as well as from monthly district reports. RESULTS: During the period under investigation, a total of 23,524 pregnant women attended their 1st antenatal care visits, of which 12,775 (54.3%) and 7581 (32.2%) received one and two doses of IPTp, respectively. In regard to ITNs, a total of 16,436 (69.9%) pregnant women received ITNs. Uptake of IPTp and ITNs by pregnant women at ANC services was higher in southern Mozambique and lower in districts situated in the northern part of the country. Stock-outs of SP and ITNs were reported in 50.0% (11/22) and 54.5% (12/22) of the health facilities, respectively. Coverage of IPTp and ITN in health facilities with stock-outs of SP and ITNs was much lower as compared to health facilities with no stock-outs. CONCLUSIONS: Altogether, data from this study shows that coverage of the 2nd dose of IPTp, as well as ITNs, was low in pregnant women attending ANC services in Mozambique. In addition, this data also shows that stock-outs of SP and ITNs were frequent and led to lower coverage of IPTp and ITN, representing a serious barrier for the accomplishment of targets. In conclusion, this study recommends that efforts should be made to improve the supply chains of SP and ITNs.

RTS,S vaccination is associated with serologic evidence of decreased exposure to Plasmodium falciparum liver- and blood-stage parasites.

The leading malaria vaccine candidate, RTS,S, targets the sporozoite and liver stages of the Plasmodium falciparum life cycle, yet it provides partial protection against disease associated with the subsequent blood stage of infection. Antibodies against the vaccine target, the circumsporozoite protein, have not shown sufficient correlation with risk of clinical malaria to serve as a surrogate for protection. The mechanism by which a vaccine that targets the asymptomatic sporozoite and liver stages protects against disease caused by blood-stage parasites remains unclear. We hypothesized that vaccination with RTS,S protects from blood-stage disease by reducing the number of parasites emerging from the liver, leading to prolonged exposure to subclinical levels of blood-stage parasites that go undetected and untreated, which in turn boosts pre-existing antibody-mediated blood-stage immunity. To test this hypothesis, we compared antibody responses to 824 P. falciparum antigens by protein array in Mozambican children 6 months after receiving a full course of RTS,S (n = 291) versus comparator vaccine (n = 297) in a Phase IIb trial. Moreover, we used a nested case-control design to compare antibody responses of children who did or did not experience febrile malaria. Unexpectedly, we found that the breadth and magnitude of the antibody response to both liver and asexual blood-stage antigens was significantly lower in RTS,S vaccinees, with the exception of only four antigens, including the RTS,S circumsporozoite antigen. Contrary to our initial hypothesis, these findings suggest that RTS,S confers protection against clinical malaria by blocking sporozoite invasion of hepatocytes, thereby reducing exposure to the blood-stage parasites that cause disease. We also found that antibody profiles 6 months after vaccination did not distinguish protected and susceptible children during the subsequent 12-month follow-up period but were strongly associated with exposure. Together, these data provide insight into the mechanism by which RTS,S protects from malaria.

Adherence to Childhood Tuberculosis Treatment in Mozambique.

Background: There is limited literature regarding adherence rates for the treatment of tuberculosis (TB) in children. We aimed to describe TB treatment outcomes and adherence as well as to evaluate associated factors to poor adherence in Mozambican children. Methods: This is a sub-study of a community TB incidence study among children <3 years of age. Incomplete adherence included the sum of lost-to-follow-up cases plus those with a delay of > 3 weeks to treatment completion. Results: Fifty TB treatments were assessed. Forty-four (88.0%) patients completed treatment, two (4.0%) died during treatment and four (8.0%) were lost to follow-up. Incomplete adherence was observed in 31.3% (15 of 48) of cases and was associated with malnutrition or history of a migrant mother. Conclusion: Although treatment outcome is overall good, there is still a significant proportion of incomplete adherence. Further larger paediatric TB cohorts and qualitative approaches are needed to assess and confirm potential factors for non-adherence.

A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.

BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial. METHODS: We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed. RESULTS: The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619.).

Prescription practices for malaria in Mozambique: poor adherence to the national protocols for malaria treatment in 22 public health facilities.

BACKGROUND: Current World Health Organization and national protocols recommend the 'test and treat' strategy for the management of uncomplicated malaria, to reduce over prescription of artemisinin-based combination treatment (ACT). Therefore, adherence to these protocols varies in different sub-Saharan African countries and no information is available for Mozambique. This study was conducted with the aim to evaluate the prescription practices of ACT in Mozambique. METHODS: Retrospective audit of medical records corresponding to the period between July and December 2011 was conducted in 22 health units across 11 provinces in Mozambique. Two health units were selected per province according to availability of laboratory data (performing microscopy and rapid diagnostics testing-RDT or RDT only) and geographic setting (rural versus urban). At each facility, demographic data, laboratory results (blood smear or RDT), and prescription of ACT were all collected from the existing records. RESULTS: Between July and December 2011, a total of 61,730 cases were tested for malaria, of which 42.7 % (26,369/61,730) were positive. A total of 35.361 patients were malaria negative, and ACT was prescribed to 72.0 % (25.448/35.361) of them. Prescription of ACT to malaria negative patients was higher in the central region of the country as compared to the northern and southern (81.1 % in the central region versus 72.4 and 63.7 % in the northern and southern, respectively, p = 0.000) and in urban settings (88.7 % in rural versus 58.0 % in urban settings, p = 0.000). Stock out of RDT was observed in six (27.3 %) of the health facilities. When no RDT was available, patients were empirically treated with ACT. CONCLUSION: Findings from this study demonstrate that health care worker's adherence to the new guidelines for malaria treatment is poor in Mozambique and prescription of ACT to malaria negative patients remains very high. Enhanced training and supervision activities, community education and external quality assurance might lead to significant improvements in the clinician's adherence to the new guideline for malaria treatment in Mozambique.

First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.

BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).

A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine.

BACKGROUND: The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes of clinical malaria. METHODS: Using data from 5,144 participants in nine phase 2 trials, we explore predictors of vaccine immunogenicity (anti-CSP antibody titres), decay in antibody titres, and the association between antibody titres and clinical outcomes. We use empirically-observed relationships between these factors to predict vaccine efficacy in a range of scenarios. RESULTS: Vaccine-induced anti-CSP antibody titres were significantly associated with age (P = 0.04), adjuvant (P <0.001), pre-vaccination anti-hepatitis B surface antigen titres (P = 0.005) and pre-vaccination anti-CSP titres (P <0.001). Co-administration with other vaccines reduced anti-CSP antibody titres although not significantly (P = 0.095). Antibody titres showed a bi-phasic decay over time with an initial rapid decay in the first three months and a second slower decay over the next three to four years. Antibody titres were significantly associated with protection, with a titre of 51 (95% Credible Interval (CrI): 29 to 85) ELISA units/ml (EU/mL) predicted to prevent 50% of infections in children. Vaccine efficacy was predicted to decline to zero over four years in a setting with entomological inoculation rate (EIR) = 20 infectious bites per year (ibpy). Over a five-year follow-up period at an EIR = 20 ibpy, we predict RTS,S will avert 1,782 cases per 1,000 vaccinated children, 1,452 cases per 1,000 vaccinated infants, and 887 cases per 1,000 infants when co-administered with expanded programme on immunisation (EPI) vaccines. Our main study limitations include an absence of vaccine-induced cellular immune responses and short duration of follow-up in some individuals. CONCLUSIONS: Vaccine-induced anti-CSP antibody titres and transmission intensity can explain variations in observed vaccine efficacy.

HIV prevalence and associated factors among married women, Mozambique, 2015: analysis of the 2015 National AIDS Indicator Survey (IMASIDA).

Introduction: epidemiological estimates from the 2021 Joint United Nations Program on HIV/AIDS (UNAIDS) emphasize the existing gender disparities, where women face a higher risk of HIV/AIDS exposure. In Mozambique, as of 2021, the HIV prevalence rate among the adult population stood at 12.5%, with an even more concerning rate of 15.4% among women of reproductive age. Methods: a cross-sectional study was carried out with secondary data from the Survey on National Indicators of Vaccination, Malaria, and HIV/AIDS (IMASIDA 2015), where we included married women, both civil marriage and common law marriage of reproductive age 15-49 years. Statistical analyses, including chi-squared tests and logistic regression models, accounting for survey design, were employed to assess associations. Results: the study findings showed that HIV prevalence was higher among married women aged 35-49 years (aOR=2.5; 95% CI: 1.3-4.6; p=0.005), those without formal education (aOR=7.7; 95% CI: 1.1-52.9; p=0.038) and those with primary education (aOR=9.8; 95% CI: 1.6-60.1; p=0.014), those who experienced domestic violence (aOR=1.8; 95% CI: 1.0-3.2; p=0.04), had an uncircumcised partner (aOR=1.9; 95% CI: 1.2-3.1; p=0.008), and had three or more lifetime sex partners (aOR=3.6; 95% CI: 2.9-7.3; p<0.001). Women who were in one lifelong union had a lower risk of HIV positivity (aOR=0.5; 96%CI: 0.3-0.8, p=0.005). Conclusion: the findings of this study highlight sociodemographic, behavioral, and violent factors associated with HIV prevalence among women. These findings underscore the importance of targeted interventions and education programs aimed at reducing HIV transmission among females and promoting safer sexual practices.

Laboratory-based evaluation of the 4th-generation AlereTM HIV Combo rapid point-of-care test.

BACKGROUND: Mozambique is a high-prevalence country for HIV and early detection of new HIV infections is crucial for control of the epidemic. We aimed to evaluate the accuracy of the 4th-generation rapid diagnostic test (RDT) AlereTM HIV Combo in detecting acute and seroconverted HIV-infection, among sexually-active women attending three clinical health centers in Maputo, Mozambique. METHODS: Women aged 14-55 years (n = 920) seeking care at the Mavalane Health Area, Maputo (February 2018-January 2019) were included, and blood specimens sampled. Sociodemographic and sexual behavior data were collected. Point-of-care HIV testing was performed using Alere DetermineTM HIV-1/2 and Uni-GoldTM HIV-1/2. All samples were also tested using Enzygnost® HIV Integral 4 and Innotest® HIV Antigen mAb in laboratory. The 4th-generation RDT AlereTM HIV Combo was evaluated on serum samples in the laboratory. Finally, Innotest® HIV Antigen mAb, Enzygnost® HIV Integral 4 (Ag/Ab), and HIV RNA quantification acted as gold standard assays in the evaluation of AlereTM HIV Combo test for HIV antigen detection (in clinical samples and in three HIV-1 seroconversion panels). RESULTS: The antibody component of the 4th generation AlereTM HIV Combo RDT demonstrated a sensitivity and specificity of 100% examining clinical samples. However, the test did not detect HIV p24 antigen in any clinical samples, while Innotest® HIV Antigen mAb, verified by Enzygnost® HIV Integral 4 (Ag/Ab) and/or HIV RNA quantification, detected HIV antigen in six clinical samples. Furthermore, the AlereTM HIV Combo RDT had a low sensitivity in the detection of HIV p24 antigen in seroconversion panels. The HIV prevalence among the examined women was 17.8%. CONCLUSIONS: The 4th-generation RDT AlereTM HIV Combo showed similar sensitivity to the 3rd-generation RDTs to detect seroconverted HIV-infections. However, the sensitivity for detection of HIV p24 antigen and diagnosing acute HIV infections, before seroconversion, was low. There is an urgent need to develop and evaluate simple and affordable POC tests with high sensitivity and specificity for diagnosing individuals with acute HIV infection in resource-limited settings with high HIV prevalence.

Prevalence of sexually transmitted infections (STIs), associations with sociodemographic and behavioural factors, and assessment of the syndromic management of vaginal discharge in women with urogenital complaints in Mozambique.

In Mozambique, sexually transmitted infections (STIs) are estimated to be prevalent, but diagnosis and treatment of curable STIs rely only on syndromic management. We examined the prevalence of four non-viral STIs and HIV-1/2, based on etiological diagnosis, associations with sociodemographic and behavioural factors, and the STI diagnostic accuracy of the vaginal discharge syndromic management in women with urogenital complaints in Maputo, Mozambique. A cross-sectional study was performed in Maputo, Mozambique, February 2018-January 2019, enrolling 924 women of reproductive age with urogenital complaints. Endocervical/vaginal swabs were sampled and chlamydia, gonorrhoea, trichomoniasis and Mycoplasma genitalium infections were diagnosed using a multiplex real-time PCR (AmpliSens; InterLabServices). Serological testing was performed for HIV-1/2. A structured questionnaire collected metadata. All data were analyzed in STATA/IC 12.1 using descriptive statistics, chi-square tests and logistic regression model. About 40% of the women were less than 24 years old, 50.8% were single, 62.1% had their sexual debut between 12 and 17 years of age, and the main complaint was vaginal discharge syndrome (85%). The prevalence of chlamydia was 15.5%, trichomoniasis 12.1%, gonorrhoea 4.0%, M. genitalium 2.1%, and HIV-1/2 22.3%. The vaginal discharge syndrome flowchart had a sensitivity of 73.0%-82.5% and a specificity of 14%-15% for the detection of any individual non-viral STI in women with urogenital complaints. In total, 19.2% of the symptomatic women with chlamydia, trichomoniasis or gonorrhoea would not be detected and accordingly treated using the vaginal discharge syndromic management (missed treatment) and 70.0% of the women would be treated despite not being infected with any of these three STIs (overtreatment). In conclusion, a high prevalence of especially chlamydia, trichomoniasis, and HIV-1/2 was found in women of childbearing age with urogenital complaints in Maputo, Mozambique. Syndromic management of vaginal discharge revealed low accuracy in the detection of STIs in symptomatic women, especially low specificity, which resulted in under-treatment of STI-positive cases and incorrect or over-treatment of women with urogenital complaints, many of whom were negative for all the non-viral STIs. Etiological diagnosis is imperative for effective management of STIs in symptomatic and asymptomatic women.