Safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in pregnant women with HIV from Gabon and Mozambique: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The cornerstone of malaria prevention in pregnancy, intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine, is contraindicated in women with HIV who are receiving co-trimoxazole prophylaxis. We assessed whether IPTp with dihydroartemisinin-piperaquine is safe and effective in reducing the risk of malaria infection in women with HIV receiving co-trimoxazole prophylaxis and antiretroviral drugs. METHODS: For this randomised, double-blind, placebo-controlled clinical trial, women with HIV attending the first antenatal care clinic visit, resident in the study area, and with a gestational age up to 28 weeks were enrolled at five sites in Gabon and Mozambique. Participants were randomly assigned (1:1) to receive either IPTp with dihydroartemisinin-piperaquine at each scheduled antenatal care visit plus daily co-trimoxazole (intervention group) or placebo at each scheduled antenatal care visit plus daily co-trimoxazole (control group). Randomisation was done centrally via block randomisation (block sizes of eight), stratified by country. IPTp was given over 3 days under direct observation by masked study personnel. The number of daily IPTp tablets was based on bodyweight and according to the treatment guidelines set by WHO (target dose of 4 mg/kg per day [range 2-10 mg/kg per day] of dihydroartemisinin and 18 mg/kg per day [range 16-27 mg/kg per day] of piperaquine given once a day for 3 days). At enrolment, all participants received co-trimoxazole (fixed combination drug containing 800 mg trimethoprim and 160 mg sulfamethoxazole) for daily intake. The primary study outcome was prevalence of peripheral parasitaemia detected by microscopy at delivery. The modified intention-to-treat population included all randomly assigned women who had data for the primary outcome. Secondary outcomes included frequency of adverse events, incidence of clinical malaria during pregnancy, and frequency of poor pregnancy outcomes. All study personnel, investigators, outcome assessors, data analysts, and participants were masked to treatment assignment. This study is registered with ClinicalTrials.gov, NCT03671109. FINDINGS: From Sept 18, 2019, to Nov 26, 2021, 666 women (mean age 28·5 years [SD 6·4]) were enrolled and randomly assigned to the intervention (n=332) and control (n=334) groups. 294 women in the intervention group and 308 women in the control group had peripheral blood samples taken at delivery and were included in the primary analysis. Peripheral parasitaemia at delivery was detected in one (<1%) of 294 women in the intervention group and none of 308 women in the control group. The incidence of clinical malaria during pregnancy was lower in the intervention group than in the control group (one episode in the intervention group vs six in the control group; relative risk [RR] 0·12, 95% CI 0·03-0·52, p=0·045). In a post-hoc analysis, the composite outcome of overall malaria infection (detected by any diagnostic test during pregnancy or delivery) was lower in the intervention group than in the control group (14 [5%] of 311 women vs 31 [10%] of 320 women; RR 0·48, 95% CI 0·27-0·84, p=0·010). The frequency of serious adverse events and poor pregnancy outcomes (such as miscarriages, stillbirths, premature births, and congenital malformations) did not differ between groups. The most frequently reported drug-related adverse events were gastrointestinal disorder (reported in less than 4% of participants) and headache (reported in less than 2% of participants), with no differences between study groups. INTERPRETATION: In the context of low malaria transmission, the addition of IPTp with dihydroartemisinin-piperaquine to co-trimoxazole prophylaxis in pregnant women with HIV did not reduce peripheral parasitaemia at delivery. However, the intervention was safe and associated with a decreased risk of clinical malaria and overall Plasmodium falciparum infection, so it should be considered as a strategy to protect pregnant women with HIV from malaria. FUNDING: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2) and Medicines for Malaria Venture. TRANSLATIONS: For the Portuguese and French translations of the abstract see Supplementary Materials section.

Retention in Care and Virological Failure among Adult HIV-Positive Patients on First-Line Antiretroviral Treatment in Maputo, Mozambique.

INTRODUCTION: Access to antiretroviral treatment (ART) is increasingly available worldwide; however, the number of patients lost to follow-up and number of treatment failures continue to challenge most African countries. OBJECTIVES: To analyse the retention in clinical care and the virological response and their associated factors of HIV-1 patients from the Maputo Military Hospital (MMH). METHODS: A cross-sectional observational study was conducted to analyse data from patients who started ART between 2016 and 2018 in the MMH. RESULTS: At the end of 12 months, 75.1% of 1247 patients were active on clinical follow-up and 16.8% had suspected virologic failure (VL > 1000 copies/mm3). Patients younger than 40 years old were more likely to be lost to follow-up when compared to those aged >50 years old, as well as patients who were unemployed and patients with a CD4 count < 350 cells/mm3. Patients with haemoglobin levels lower than 10 g/dL and with a CD4 count < 350 cells/mm3 were more likely to have virological failure. CONCLUSIONS: We have identified clinical and sociodemographic determinants of loss to follow-up and in the development of virological failure for HIV-positive patients in clinical care in the MMH. Therefore, HIV programs must consider these factors to increase the screening of patients at high risk of poor outcomes and particularly to strengthen adherence counselling programs.

Antimicrobial resistance and clonality of Staphylococcus aureus causing bacteraemia in children admitted to the Manhiça District Hospital, Mozambique, over two decades.

Background: Staphylococcus aureus is one of the main causes of bacteraemia, associated with high mortality, mainly due to the occurrence of multidrug resistant (MDR) strains. Data on antibiotic susceptibility and genetic lineages of bacteraemic S. aureus are still scarce in Mozambique. The study aims to describe the antibiotic susceptibility and clonality of S. aureus isolated from blood cultures of children admitted to the Manhiça District Hospital over two decades (2001-2019). Methods: A total of 336 S. aureus isolates detected in blood cultures of children aged <5 years were analyzed for antibiotic susceptibility by disk diffusion or minimal inhibitory concentration, and for the presence of resistance determinants by PCR. The clonality was evaluated by SmaI-PFGE, spa typing, and MLST. The SCCmec element was characterized by SCCmec typing. Results: Most S. aureus (94%, 317/336) were resistant to at least one class of antibiotics, and one quarter (25%) showed a MDR phenotype. High rates of resistance were detected to penicillin (90%) and tetracycline (48%); followed by erythromycin/clindamycin (25%/23%), and co-trimoxazole (11%), while resistance to methicillin (MRSA strains) or gentamicin was less frequent (≤5%). The phenotypic resistance to distinct antibiotics correlated well with the corresponding resistance determinants (Cohen's κ test: 0.7-1.0). Molecular typing revealed highly diverse clones with predominance of CC5 (17%, 58/336) and CC8 (16%), followed by CC15 (11%) and CC1 (11%). The CC152, initially detected in 2001, re-emerged in 2010 and became predominant throughout the remaining surveillance period, while other CCs (CC1, CC5, CC8, CC15, CC25, CC80, and CC88) decreased over time. The 16 MRSA strains detected belonged to clones t064-ST612/CC8-SCCmecIVd (69%, 11/16), t008-ST8/CC8-SCCmecNT (25%, 4/16) and t5351-ST88/CC88-SCCmecIVa (6%, 1/16). Specific clonal lineages were associated with extended length of stay and high in-hospital mortality. Conclusion: We document the circulation of diverse MDR S. aureus causing paediatric bacteraemia in Manhiça district, Mozambique, requiring a prompt recognition of S. aureus bacteraemia by drug resistant clones to allow more targeted clinical management of patients.

Reasons for non-disclosure of HIV-Positive status to healthcare providers: a mixed methods study in Mozambique.

BACKGROUND: Non-disclosure of known HIV status by people living with HIV but undergoing HIV testing leads to waste of HIV testing resources and distortion of estimates of HIV indicators. In Mozambique, an estimated one-third of persons who tested positive already knew their HIV-positive status. To our knowledge, this study is the first to assess the factors that prevent people living with HIV (PLHIV) from disclosing their HIV-positive status to healthcare providers during a provider-initiated counseling and testing (PICT) campaign. METHODS: This analysis was nested in a larger PICT cross-sectional study performed in the Manhiça District, Southern Mozambique from January to July 2019, in which healthcare providers actively asked patients about their HIV-status. Patients who tested positive for HIV were crosschecked with the hospital database to identify those who had previously tested positive and were currently or previously enrolled in care. PLHIV who did not disclose their HIV-positive status were invited to participate and provide consent, and were interviewed using a questionnaire designed to explore barriers, patterns of community/family disclosure, and stigma and discrimination. RESULTS: We found that 16.1% of participants who tested positive during a PICT session already knew their HIV-positive status but did not disclose it to the healthcare provider. All the participants reported previous mistreatment by general healthcare providers as a reason for nondisclosure during PICT. Other reasons included the desire to know if they were cured (33.3%) or to re-engage in care (23.5%). Among respondents, 83.9% reported having disclosed their HIV-status within their close community, 48.1% reported being victims of verbal or physical discrimination following their HIV diagnosis, and 46.7% reported that their HIV status affected their daily activities. CONCLUSION: Previous mistreatment by healthcare workers was the main barrier to disclosing HIV-positive status. The high proportion of those disclosing their HIV status to their community but not to healthcare providers suggests that challenges with patient-provider relationships affect this care behavior rather than social stigma and discrimination. Improving patient-provider relationships could increase trust in healthcare providers, reduce non-disclosures, and help optimize resources and provide accurate estimates of the UNAIDS first 95 goal.

Genomic characterization of the rotavirus G3P[8] strain in vaccinated children, reveals possible reassortment events between human and animal strains in Manhiça District, Mozambique.

Mozambique introduced the rotavirus vaccine (Rotarix®; GlaxoSmithKline Biologicals, Rixensart, Belgium) in 2015, and since then, the Centro de Investigação em Saúde de Manhiça has been monitoring its impact on rotavirus-associated diarrhea and the trend of circulating strains, where G3P[8] was reported as the predominant strain after the vaccine introduction. Genotype G3 is among the most commonly detected Rotavirus strains in humans and animals, and herein, we report on the whole genome constellation of G3P[8] detected in two children (aged 18 months old) hospitalized with moderate-to-severe diarrhea at the Manhiça District Hospital. The two strains had a typical Wa-like genome constellation (I1-R1-C1-M1-A1-N1-T1-E1-H1) and shared 100% nucleotide (nt) and amino acid (aa) identities in 10 gene segments, except for VP6. Phylogenetic analysis demonstrated that genome segments encoding VP7, VP6, VP1, NSP3, and NSP4 of the two strains clustered most closely with porcine, bovine, and equine strains with identities ranging from 86.9-99.9% nt and 97.2-100% aa. Moreover, they consistently formed distinct clusters with some G1P[8], G3P[8], G9P[8], G12P[6], and G12P[8] strains circulating from 2012 to 2019 in Africa (Mozambique, Kenya, Rwanda, and Malawi) and Asia (Japan, China, and India) in genome segments encoding six proteins (VP2, VP3, NSP1-NSP2, NSP5/6). The identification of segments exhibiting the closest relationships with animal strains shows significant diversity of rotavirus and suggests the possible occurrence of reassortment events between human and animal strains. This demonstrates the importance of applying next-generation sequencing to monitor and understand the evolutionary changes of strains and evaluate the impact of vaccines on strain diversity.

Using testing history to estimate HIV incidence in mothers living in resource-limited settings: Maximizing efficiency of a community health survey in Mozambique.

Obtaining rapid and accurate HIV incidence estimates is challenging because of the need for long-term follow-up for a large cohort. We estimated HIV incidence among women who recently delivered in southern Mozambique by leveraging data available in routine health cards. A cross-sectional household HIV-testing survey was conducted from October 2017 to April 2018 among mothers of children born in the previous four years in the Manhiça Health Demographic Surveillance System area. Randomly-selected mother-child pairs were invited to participate and asked to present documentation of their last HIV test result. HIV-testing was offered to mothers with no prior HIV-testing history, or with negative HIV results obtained over three months ago. HIV incidence was estimated as the number of mothers newly diagnosed with HIV per total person-years, among mothers with a prior documented HIV-negative test. Among 5000 mother-child pairs randomly selected, 3069 were interviewed, and 2221 reported a previous HIV-negative test. From this group, we included 1714 mothers who had taken a new HIV test during the survey. Most of mothers included (83.3%,1428/1714) had a previous documented HIV test result and date. Median time from last test to survey was 15.5 months (IQR:8.0-25.9). A total of 57 new HIV infections were detected over 2530.27 person-years of follow-up. The estimated HIV incidence was 2.25 (95% CI: 1.74-2.92) per 100 person-years. Estimating HIV incidence among women who recently delivered using a community HIV-focused survey coupled with previous HIV-testing history based on patients' clinical documents is an achievable strategy.

Prevalence and impact of SARS-CoV-2 infection on maternal and infant health in African populations: protocol of a multicentre prospective cohort study (MA-CoV project).

INTRODUCTION: Pregnant women are currently considered a vulnerable population to SARS-CoV-2 infection, with increased risk of severe COVID-19, preterm birth and maternal mortality. There is, however, a paucity of data on the burden of maternal SARS-CoV-2 infection in sub-Saharan countries. The objective of this study is to determine the prevalence and health effects of maternal SARS-CoV-2 infection in selected sites from Gabon and Mozambique. METHODS AND ANALYSIS: MA-CoV (MAternal CoVid) is an observational, multicentre prospective cohort study where 1000 pregnant women (500 per country) will be enrolled at the antenatal clinic visits. Participants will undergo monthly follow-up at each antenatal care visit, delivery and postpartum visit. The primary study outcome is the prevalence of SARS-CoV-2 infection during pregnancy. The clinical presentation of COVID-19 in pregnancy will also be characterised, and incidence of infection during pregnancy will be evaluated, as well as the risk factors of maternal and neonatal morbidity and mortality associated with SARS-CoV-2 infection and the risk of mother to child transmission of SARS-CoV-2. SARS-CoV-2 infection screening will be performed through PCR diagnosis. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the Comité National d'Éthique pour la Recherche au Gabon, Comité Nacional de Bioética para Saúde de Moçambique and the Ethics Committee of the Hospital Clinic of Barcelona (Spain). Project results will be presented to all stakeholders and published in open access journals. TRIAL REGISTRATION NUMBER: NCT05303168.

Epidemiology and clinical presentation of community-acquired Staphylococcus aureus bacteraemia in children under 5 years of age admitted to the Manhiça District Hospital, Mozambique, 2001-2019.

Staphylococcus aureus bacteraemia (SAB) is one of the most common bloodstream infections globally. Data on the burden and epidemiology of community-acquired SAB in low-income countries are scarce but needed to define preventive and management strategies. Blood samples were collected from children < 5 years of age with fever or severe disease admitted to the Manhiça District Hospital for bacterial isolation, including S. aureus. Between 2001 and 2019, 7.6% (3,197/41,891) of children had bacteraemia, of which 12.3% corresponded to SAB. The overall incidence of SAB was 56.1 episodes/100,000 children-years at risk (CYAR), being highest among neonates (589.8 episodes/100,000 CYAR). SAB declined significantly between 2001 and 2019 (322.1 to 12.5 episodes/100,000 CYAR). In-hospital mortality by SAB was 9.3% (31/332), and significantly associated with infections by multidrug-resistant (MDR) strains (14.7%, 11/75 vs. 6.9%, 14/204 among non-MDR, p = 0.043) and methicillin-resistant S. aureus (33.3%, 5/15 vs. 7.6%, 20/264 among methicillin-susceptible S. aureus, p = 0.006). Despite the declining rates of SAB, this disease remains an important cause of death among children admitted to MDH, possibly in relation to the resistance to the first line of empirical treatment in use in our setting, suggesting an urgent need to review current policy recommendations.

SARS-CoV-2 Seropositivity and HIV Viral Load Among Mozambican Pregnant Women.

INTRODUCTION: Prevalence estimates of SARS-CoV-2 infection in Africa are limited, particularly among pregnant women and in those living with HIV. This study assessed the seroprevalence of SARS-CoV-2 antibodies among Mozambican HIV-infected pregnant women during the first year of the pandemic, before COVID-19 vaccines were deployed in the country. SETTING: The study was conducted in Manhiça district, a semirural area in southern Mozambique. METHODS: A prospective cohort study including pregnant women living with HIV was conducted from November 2019 to June 2021. Women were enrolled at the first antenatal care clinic visit and followed until postpartum. HIV viral load and IgM/IgG antibodies against SARS-CoV-2 were determined in blood samples at first antenatal care clinic visit and at delivery. Associations between SARS-CoV-2 serostatus and maternal characteristics at enrolment were analyzed. RESULTS: A total of 397 women were enrolled. SARS-CoV-2 IgG/IgM antibodies were detected in 7.1% of women at enrolment and in 8.5% of women at delivery. Overall, SARS-CoV-2 antibodies were detected in 45 women (11.3%; 95% confidence interval 8.4 to 14.9%) during the study period; the first seropositive sample was identified in September 2020. Having undetectable HIV viral load was associated with seropositivity of SARS-CoV-2 IgG/IgM [odds ratio 3.35 (1.10 to 11.29); P = 0.039]. CONCLUSION: Seroprevalence of SARS-CoV-2 antibodies in this cohort of Mozambican unvaccinated pregnant women was similar to reported global estimates of approximately 10% in pregnancy for 2021. The findings also suggest that pregnant women with high HIV viral load may have an impaired immune response against SARS-CoV-2 and might need to be carefully managed in case of COVID-19.

Machine learning outperformed logistic regression classification even with limit sample size: A model to predict pediatric HIV mortality and clinical progression to AIDS.

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression.

Impact of rotavirus vaccination on diarrheal hospitalizations in children younger than 5 years of age in a rural southern Mozambique.

BACKGROUND: Rotavirus vaccine(Rotarix®) was introduced in Mozambique through its Expanded Program of Immunization in September 2015. We assessed the impact of rotavirus vaccination on childhood gastroenteritis-associated hospitalizations post-vaccine introduction in a high HIV prevalence rural setting of southern Mozambique. METHODS: We reviewed and compared the trend of hospitalizations (prevalence) and incidence rates of acute gastroenteritis (AGE), and rotavirus associated-diarrhea (laboratory confirmed rotavirus) in pre- (January 2008-August 2015) and post-rotavirus vaccine introduction periods (September 2015-December 2020), among children <5 years of age admitted to Manhiça District Hospital. RESULTS: From January 2008 to December 2020, rotavirus vaccination was found to contribute to the decline of the prevalence of AGE from 19% (95% CI: 18.14-20.44) prior to the vaccine introduction to 10% (95% CI: 8.89-11.48) in the post-introduction period, preventing 40% (95 % IE: 38-42) and 84% (95 % IE: 80-87) of the expected AGE and laboratory confirmed rotavirus cases, respectively, among infants. Similarly, the overall incidence of rotavirus was 11.8-fold lower in the post-vaccine introduction period (0.4/1000 child-years-at-risk [CYAR]; 95% CI: 0.3-0.6) compared with the pre-vaccination period (4.7/1000 CYAR; 95% CI: 4.2-5.1) with the highest reduction being observed among infants (16.8-fold lower from the 15.1/1000 CYAR in the pre-vaccine to 0.9/1000 CYAR in the post-vaccine eras). CONCLUSIONS: We documented a significant reduction in all-cause diarrhea hospitalizations and rotavirus positivity after vaccine introduction demonstrating the beneficial impact of rotavirus vaccination in a highly vulnerable population.

Burden, clinical presentation and risk factors of advanced HIV disease in pregnant Mozambican women.

BACKGROUND: Information on the frequency and clinical features of advanced HIV disease (AHD) in pregnancy and its effects on maternal and perinatal outcomes is limited. The objective of this study was to describe the prevalence and clinical presentation of AHD in pregnancy, and to assess the impact of AHD in maternal and perinatal outcomes in Mozambican pregnant women. METHODS: This is a prospective and retrospective cohort study including HIV-infected pregnant women who attended the antenatal care (ANC) clinic at the Manhiça District Hospital between 2015 and 2020. Women were followed up for 36 months. Levels of CD4 + cell count were determined to assess AHD immune-suppressive changes. Risk factors for AHD were analyzed and the immune-suppressive changes over time and the effect of AHD on pregnancy outcomes were assessed. RESULTS: A total of 2458 HIV-infected pregnant women were enrolled. The prevalence of AHD at first ANC visit was 14.2% (349/2458). Among women with AHD at enrolment, 76.2% (260/341) were on antiretroviral therapy (ART). The proportion of women with AHD increased with age reaching 20.5% in those older than 35 years of age (p < 0.001). Tuberculosis was the only opportunistic infection diagnosed in women with AHD [4.9% (17/349)]. There was a trend for increased CD4 + cell count in women without AHD during the follow up period; however, in women with AHD the CD4 + cell count remained below 200 cells/mm3 (p < 0.001). Forty-two out of 2458 (1.7%) of the women were severely immunosuppressed (CD4 + cell count < 50 cells/mm3). No significant differences were detected between women with and without AHD in the frequency of maternal mortality, preterm birth, low birth weight and neonatal HIV infection. CONCLUSIONS: After more than two decades of roll out of ART in Mozambique, over 14% and nearly 2% of HIV-infected pregnant women present at first ANC clinic visit with AHD and severe immunosuppression, respectively. Prompt HIV diagnosis in women of childbearing age, effective linkage to HIV care with an optimal ART regimen and close monitoring after ART initiation may contribute to reduce this burden and improve maternal and child survival.

Prompt HIV diagnosis and antiretroviral treatment in postpartum women is crucial for prevention of mother to child transmission during breastfeeding: Survey results in a high HIV prevalence community in southern Mozambique after the implementation of Option B.

OBJECTIVE: World Health Organization recommends promoting breastfeeding without restricting its duration among HIV-positive women on lifelong antiretroviral treatment (ART). There is little data on breastfeeding duration and mother to child transmission (MTCT) beyond 24 months. We compared the duration of breastfeeding in HIV-exposed and HIV-unexposed children and we identified factors associated with postpartum-MTCT in a semi-rural population of Mozambique. METHODS: This cross-sectional assessment was conducted from October-2017 to April-2018. Mothers who had given birth within the previous 48-months in the Manhiça district were randomly selected to be surveyed and to receive an HIV-test along with their children. Postpartum MTCT was defined as children with an initial HIV positive result beyond 6 weeks of life who initiated breastfeeding if they had a first negative PCR result during the first 6 weeks of life or whose mother had an estimated date of infection after the child's birth. Cumulative incidence accounting for right-censoring was used to compare breastfeeding duration in HIV-exposed and unexposed children. Fine-Gray regression was used to assess factors associated with postpartum-MTCT. RESULTS: Among the 5000 mother-child pairs selected, 69.7% (3486/5000) were located and enrolled. Among those, 27.7% (967/3486) children were HIV-exposed, 62.2% (2169/3486) were HIV-unexposed and for 10.0% (350/3486) HIV-exposure was unknown. Median duration of breastfeeding was 13.0 (95%CI:12.0-14.0) and 20.0 (95%CI:19.0-20.0) months among HIV-exposed and HIV-unexposed children, respectively (p<0.001). Of the 967 HIV-exposed children, 5.3% (51/967) were HIV-positive at the time of the survey. We estimated that 27.5% (14/51) of the MTCT occurred during pregnancy and delivery, 49.0% (2551) postpartum-MTCT and the period of MTCT remained unknown for 23.5% (12/51) of children. In multivariable analysis, mothers' ART initiation after the date of childbirth was associated (aSHR:9.39 [95%CI:1.75-50.31], p = 0.001), however breastfeeding duration was not associated with postpartum-MTCT (aSHR:0.99 [95%CI:0.96-1.03], p = 0.707). CONCLUSION: The risk for postpartum MTCT was nearly tenfold higher in women newly diagnosed and/or initiating ART postpartum. This highlights the importance of sustained HIV screening and prompt ART initiation in postpartum women in Sub-Saharan African countries. Under conditions where HIV-exposed infants born to mothers on ART receive adequate PMTCT, extending breastfeeding duration may be recommended.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence.

BACKGROUND: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. METHODS: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. RESULTS: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. CONCLUSIONS: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

The epidemiology of severe malaria at Manhiça District Hospital, Mozambique: a retrospective analysis of 20 years of malaria admissions surveillance data.

BACKGROUND: Most malaria burden estimates rely on modelling infection prevalence to case incidence data, with insufficient attention having been paid to the changing clinical presentation of severe disease and its relationship with changing transmission intensity. We present 20 years of longitudinal surveillance data to contribute to the understanding of the relationship between malaria transmission and the burden and clinical presentation of severe malaria and to inform policy. METHODS: This retrospective analysis of clinical surveillance hospital data included all children younger than 15 years admitted with malaria to Manhiça District Hospital (MDH), Mozambique, from July 1, 1997, to June 30, 2017. Case fatality ratios (CFRs) were calculated as the number of patients who died having a specific diagnosis or syndrome divided by the total number of patients with known outcome admitted with that diagnosis or syndrome. FINDINGS: Over the study period, 32 138 children were admitted to MDH with a malaria diagnosis. Malaria accounted for a large proportion of admissions, ranging from 4083 (76·9%) of 5307 admissions in 2000-01 to 706 (27·5%) of 2568 admissions in 2010-11. Since 2000-02, the absolute and relative number of malaria admissions and deaths presented a decreasing trend. The age pattern of patients with malaria shifted to older ages with a median age of 1·7 years (IQR 0·9-3·0) in 1997-2006 and 2·6 years (IQR 1·3-4·4) in 2006-17, although most malaria deaths (60-88% in 2009-17) still occurred in children younger than 5 years. The clinical presentation of severe malaria changed, with an increase in cerebral malaria and a decrease in severe anaemia and respiratory distress, leading to similar yearly cases for the three syndromes. CFRs for severe malaria fluctuated between 1·1% (2 of 186 in 2014-15) and 7·2% (11 of 152 in 2010-11), varying by severe malaria syndrome (3·3% [70 of 2105] for severe anaemia, 5·1% [191 of 3777] for respiratory distress, and 14·8% [72 of 487] for cerebral malaria). Overall malaria CFRs (1·8% [543 of 30 163]) did not vary by age group. INTERPRETATION: Despite the unprecedented scale up of malaria control tools, malaria still represented around 30-40% of paediatric hospital admissions in 2006-17. The age shift towards older children was not accompanied by an increase in severe malaria or deaths; however, control programmes should consider adapting their high-risk target groups to include older children. Malaria remains a leading cause of disease and health-care system use and the massive unfinished malaria control agenda warrants intensified efforts. FUNDING: Spanish Agency for International Cooperation and Development.

Molecular Epidemiology of Rotavirus Strains in Symptomatic and Asymptomatic Children in Manhiça District, Southern Mozambique 2008-2019.

Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix®) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction.

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.

The impact of the caregiver mobility on child HIV care in the Manhiça District, Southern Mozambique: A clinical based study.

INTRODUCTION: Manhiça District, in Southern Mozambique harbors high HIV prevalence and a long history of migration. To optimize HIV care, we sought to assess how caregiver's mobility impacts children living with HIV (CLHIV)´s continuation in HIV care and to explore the strategies used by caregivers to maintain their CLHIV on antiretroviral treatment (ART). METHODS: A clinic-based cross-sectional survey conducted at the Manhiça District Hospital between December-2017 and February-2018. We enrolled CLHIV with a self-identified migrant caregiver (moved outside of Manhiça District ≤12 months prior to survey) and non-migrant caregiver, matched by the child age and sex. Survey data were linked to CLHIV clinical records from the HIV care and treatment program. RESULTS: Among the 975 CLHIV screened, 285 (29.2%) were excluded due to absence of an adult at the appointment. A total of 232 CLHIV-caregiver pairs were included. Of the 41 (35%) CLHIV migrating with their caregivers, 38 (92.6%) had access to ART at the destination because either the caregivers travelled with it 24 (63%) or it was sent by a family member 14 (36%). Among the 76 (65%) CLHIV who did not migrate with their caregivers, for the purpose of pharmacy visits, 39% were cared by their grandfather/grandmother, 28% by an aunt/uncle and 16% by an adult brother/sister. CLHIV of migrant caregivers had a non-statistically significant increase in the number of previous reported sickness episodes (OR = 1.38, 95%CI: 0.79-2.42; p = 0.257), ART interruptions (OR = 1.73; 95%CI: 0.82-3.63; p = 0.142) and lost-to-follow-up episodes (OR = 1.53; 95%CI: 0.80-2.94; p = 0.193). CONCLUSIONS: Nearly one third of the children attend their HIV care appointments unaccompanied by an adult. The caregiver mobility was not found to significantly affect child's retention on ART. Migrant caregivers adopted strategies such as the transportation of ART to the mobility destination to avoid impact of mobility on the child's HIV care. However this may have implications on ART stability and effectiveness that should be investigated in rural areas.

Evaluation of the safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in HIV-infected pregnant women: protocol of a multicentre, two-arm, randomised, placebo-controlled, superiority clinical trial (MAMAH project).

INTRODUCTION: Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin-piperaquine (DHA-PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial's objective is to determine if monthly 3-day IPTp courses of DHA-PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy. METHODS AND ANALYSIS: This is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA-PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria. ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals. TRIAL REGISTRATION NUMBER: NCT03671109.