RESUMEN
BACKGROUND: Low-density Plasmodium falciparum infections prevail in low transmission settings, where immunity is expected to be minimal, suggesting an immune-independent effect on parasite densities. We aimed to describe parasite densities in pregnancy, and determine how gravidity and antibody-mediated immunity affect these, during a period of declining malaria transmission in southern Mozambique. METHODS: We documented P. falciparum infections at first antenatal care visits (n = 6471) between November 2016 and October 2019 in Ilha Josina (high-to-moderate transmission area), Manhiça (low transmission area), and Magude (pre-elimination area). Two-way interactions in mixed-effects regression models were used to assess gravidity-dependent differences in quantitative PCR-determined P. falciparum positivity rates (PfPRqPCR) and densities, in the relative proportion of detectable infections (pDi) with current diagnostic tests (≥ 100 parasites/µL) and in antimalarial antibodies. RESULTS: PfPRqPCR declined from 28 to 13% in Ilha Josina and from 5-7 to 2% in Magude and Manhiça. In primigravidae, pDi was highest in Ilha Josina at the first study year (p = 0.048), which declined with falling PfPRqPCR (relative change/year: 0.41, 95% CI [0.08; 0.73], p = 0.029), with no differences in antibody levels. Higher parasite densities in primigravidae from Ilha Josina during the first year were accompanied by a larger reduction of maternal hemoglobin levels (- 1.60, 95% CI [- 2.49; - 0.72; p < 0.001), than in Magude (- 0.76, 95% CI [- 1.51; - 0.01]; p = 0.047) and Manhiça (- 0.44, 95% CI [- 0.99; 0.10; p = 0.112). In contrast, multigravidae during the transmission peak in Ilha Josina carried the lowest pDi (p = 0.049). As PfPRqPCR declined, geometric mean of parasite densities increased (4.63, 95% CI [1.28; 16.82], p = 0.020), and antibody levels declined among secundigravidae from Ilha Josina. CONCLUSIONS: The proportion of detectable and clinically relevant infections is the highest in primigravid women from high-to-moderate transmission settings and decreases with declining malaria. In contrast, the falling malaria trends are accompanied by increased parasite densities and reduced humoral immunity among secundigravidae. Factors other than acquired immunity thus emerge as potentially important for producing less detectable infections among primigravidae during marked declines in malaria transmission.
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Antimaláricos , Malaria Falciparum , Humanos , Femenino , Embarazo , Número de Embarazos , Plasmodium falciparum , Estudios Prospectivos , Malaria Falciparum/tratamiento farmacológico , Antimaláricos/uso terapéutico , PrevalenciaRESUMEN
BACKGROUND: HIV-infected individuals on antiretroviral therapy (ART) require treatment with artemisinin-based combination therapy (ACT) when infected with malaria. Dihydroartemisinin-piperaquine (DPQ) is recommended for treatment of Plasmodium falciparum malaria, but its efficacy and safety has not been evaluated in HIV-infected individuals on ART, among whom drug-drug interactions are expected. Day-42 adequate clinical and parasitological response (ACPR) and incidence of adverse events were assessed in HIV-infected individuals on non-nucleoside reverse transcriptase inhibitor-based ART (efavirenz and nevirapine) with uncomplicated P. falciparum malaria treated with dihydroartemisinin-piperaquine. METHODS: An open label single arm clinical trial was conducted in Malawi (Blantyre and Chikhwawa districts) and Mozambique (Manhiça district) involving patients aged 15-65 years with uncomplicated P. falciparum malaria who were on efavirenz-based or nevirapine-based ART. They received a directly-observed 3-day standard treatment of DPQ and were followed up until day 63 for malaria infection and adverse events. Day-42 PCR-corrected-ACPRs (95% confidence interval [CI]) were calculated for the intention-to-treat (ITT) population. RESULTS: The study enrolled 160 and 61 patients on efavirenz and nevirapine-based ART, with a baseline geometric mean (95% CI) parasite density of 2681 (1964-3661) and 9819 (6606-14,593) parasites/µL, respectively. The day-42 PCR-corrected ACPR (95% CI) was 99.4% (95.6-99.9%) in the efavirenz group and 100% in the nevirapine group. Serious adverse events occurred in 5.0% (8/160) and 3.3% (2/61) of the participants in the efavirenz and nevirapine group, respectively, but none were definitively attributable to DPQ. Cases of prolonged QT interval (> 60 ms from baseline) occurred in 31.2% (48/154) and 13.3% (8/60) of the patients on the efavirenz and nevirapine ART groups, respectively. These were not clinically significant and resolved spontaneously over time. As this study was not designed to compare the efficacy and safety of DPQ in the two ART groups, no formal statistical comparisons were made between the two ART groups. CONCLUSIONS: DPQ was highly efficacious and safe for the treatment of malaria in HIV-infected patients concurrently taking efavirenz- or nevirapine-based ART, despite known pharmacokinetic interactions between dihydroartemisinin-piperaquine and efavirenz- or nevirapine-based ART regimens. Trial registration Pan African Clinical Trials Registry (PACTR): PACTR201311000659400. Registered on 4 October 2013, https://pactr.samrc.ac.za/Search.aspx.
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Antirretrovirales/uso terapéutico , Antimaláricos/efectos adversos , Artemisininas/efectos adversos , Malaria Falciparum/prevención & control , Quinolinas/efectos adversos , Adolescente , Adulto , Alquinos , Benzoxazinas/uso terapéutico , Ciclopropanos , Combinación de Medicamentos , Femenino , Humanos , Malaui , Masculino , Persona de Mediana Edad , Mozambique , Nevirapina/uso terapéutico , Plasmodium falciparum/fisiología , Adulto JovenRESUMEN
INTRODUCTION: Retention in care and reengagement of lost to follow-up (LTFU) patients are priority challenges in pediatric HIV care. We aimed to assess whether a telephone-call active tracing program facilitated reengagement in care (RIC) in the Manhiça District Hospital, Mozambique. METHODS: Telephone tracing of LTFU children was performed from July 2016 to March 2017. Both ART (antiretroviral treatment) and preART patients were included in this study. LTFU was defined as not attending the clinic for ≥120 days after last attended visit. Reengagement was determined 3 months after an attempt to contact. RESULTS: A total of 144 children initially identified as LTFU entered the active tracing program and 37 were reached by means of telephone tracing. RIC was 57% (95% CI, 39-72%) among children who could be reached versus 18% (95% CI, 11-26%) of those who could not be reached (p = 0.001). CONCLUSION: Telephone tracing could be an effective tool for facilitating reengagement in pediatric HIV care. However, the difficulty of reaching patients is an obstacle that can undermine the program.
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Fármacos Anti-VIH/uso terapéutico , Teléfono Celular , Atención a la Salud/organización & administración , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Perdida de Seguimiento , Retención en el Cuidado/estadística & datos numéricos , Adulto , Instituciones de Atención Ambulatoria , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Mozambique , Evaluación de Programas y Proyectos de Salud , Factores de Riesgo , Resultado del TratamientoRESUMEN
Background: A main criterion to identify malaria vaccine candidates is the proof that acquired immunity against them is associated with protection from disease. The age of the studied individuals, heterogeneous malaria exposure, and assumption of the maintenance of a baseline immune response can confound these associations. Methods: Immunoglobulin G/immunoglobulin M (IgG/ IgM) levels were measured by Luminex® in Mozambican children monitored for clinical malaria from birth until 3 years of age, together with functional antibodies. Studied candidates were pre-erythrocytic and erythrocytic antigens, including EBAs/PfRhs, MSPs, DBLs, and novel antigens merely or not previously studied in malaria-exposed populations. Cox regression models were estimated at 9 and 24 months of age, accounting for heterogeneous malaria exposure or limiting follow-up according to the antibody's decay. Results: Associations of antibody responses with higher clinical malaria risk were avoided when accounting for heterogeneous malaria exposure or when limiting the follow-up time in the analyses. Associations with reduced risk of clinical malaria were found only at 24 months old, but not younger children, for IgG breadth and levels of IgG targeting EBA140III-V, CyRPA, DBL5ε and DBL3x, together with C1q-fixation activity by antibodies targeting MSP119. Conclusions: Malaria protection correlates were identified, only in children aged 24 months old when accounting for heterogeneous malaria exposure. These results highlight the relevance of considering age and malaria exposure, as well as the importance of not assuming the maintenance of a baseline immune response throughout the follow-up. Results may be misleading if these factors are not considered.
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Anticuerpos Antiprotozoarios/inmunología , Inmunoglobulina G/inmunología , Malaria Falciparum/inmunología , Inmunidad Adaptativa , Factores de Edad , Antígenos de Protozoos/inmunología , Preescolar , Femenino , Humanos , Inmunoglobulina M/inmunología , Lactante , Recién Nacido , Vacunas contra la Malaria/inmunología , Malaria Falciparum/prevención & control , Masculino , Mozambique , Plasmodium falciparum , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de RegresiónRESUMEN
BACKGROUND: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known. METHODS: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012. We used microscopic and histologic examination and a quantitative polymerase-chain-reaction (qPCR) assay, as well as flow-cytometric analysis of IgG antibody responses against two parasite lines. RESULTS: Positive qPCR tests for P. falciparum decreased from 33% in 2003 to 2% in 2010 and increased to 6% in 2012, with antimalarial IgG antibody responses mirroring these trends. Parasite densities in peripheral blood on qPCR assay were higher in 2010-2012 (geometric mean [±SD], 409±1569 genomes per microliter) than in 2003-2005 (44±169 genomes per microliter, P=0.02), as were parasite densities in placental blood on histologic assessment (50±39% of infected erythrocytes vs. 4±6%, P<0.001). The malaria-associated reduction in maternal hemoglobin levels was larger in 2010-2012 (10.1±1.8 g per deciliter in infected women vs. 10.9±1.7 g per deciliter in uninfected women; mean difference, -0.82 g per deciliter; 95% confidence interval [CI], -1.39 to -0.25) than in 2003-2005 (10.5±1.1 g per deciliter vs. 10.6±1.5 g per deciliter; difference, -0.12 g per deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth weight (2863±440 g in women with past or chronic infections vs. 3070±482 g in uninfected women in 2010-2012; mean difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994±487 g vs. 3117±455 g in 2003-2005; difference, -44.8 g; 95% CI, -139.1 to 49.5). CONCLUSIONS: Antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria. (Funded by Malaria Eradication Scientific Alliance and others.).
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Anticuerpos Antiprotozoarios/sangre , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Complicaciones Infecciosas del Embarazo/epidemiología , Adulto , Costo de Enfermedad , Femenino , Humanos , Inmunoglobulina G/sangre , Malaria Falciparum/clasificación , Mozambique/epidemiología , Carga de Parásitos , Paridad , Plasmodium falciparum/aislamiento & purificación , Embarazo , Complicaciones Infecciosas del Embarazo/clasificación , Complicaciones Infecciosas del Embarazo/inmunología , Prevalencia , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Achieving effective antiretroviral treatment (ART) monitoring is a key determinant to ensure viral suppression and reach the UNAIDS 90-90-90 targets. The gold standard for detecting virological failure is plasma human immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its availability is very limited in low-income countries due to cost and operational constraints. METHODS: HIV-1-infected adults on first-line ART attending routine visits at the Manhiça District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-γ-inducible protein 10 (IP-10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was used to build an IP-10-based model able to identify individuals with VL >150 copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model training and 63 (20%) for validation. Receiver operating characteristic curves were employed to evaluate model prediction. RESULTS: From the individuals included in the training set, 34% had detectable VL. Mean age was 41 years, 70% were females, and median time on ART was 3.4 years. IP-10 levels were significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate model demonstrated high classification performance (area under the curve = 0.85 [95% confidence interval {CI}, .80-.90]). Using a cutoff value of IP-10 ≥44.2 pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%-96.7%) and 59.9% specificity (95% CI, 52.0%-67.4%), values confirmed in the validation set. CONCLUSIONS: IP-10 is an accurate biomarker to screen individuals on ART for detectable viremia. Further studies should evaluate the benefits of IP-10 as a triage approach to monitor ART in resource-limited settings.
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Quimiocina CXCL10/sangre , Infecciones por VIH/diagnóstico , Infecciones por VIH/virología , ARN Viral/sangre , Adulto , Antirretrovirales/uso terapéutico , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Masculino , Mozambique , Curva ROC , Resultado del Tratamiento , Carga Viral , Viremia/diagnóstico , Viremia/tratamiento farmacológico , Viremia/virologíaRESUMEN
BACKGROUND: Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria transmission. METHODS: P. falciparum at delivery was assessed by microscopy, quantitative PCR (qPCR) and placental histology in 946 HIV-uninfected and 768 HIV-infected pregnant women from Benin, Gabon, Kenya and Mozambique. Resistance was defined by the proportion of submicroscopic infections and the levels of anti-parasite antibodies quantified by Luminex, and tolerance by the relationship of pregnancy outcomes with parasite densities at delivery. RESULTS: P. falciparum prevalence by qPCR in peripheral and/or placental blood of HIV-uninfected Mozambican, Gabonese and Beninese women at delivery was 6% (21/340), 11% (28/257) and 41% (143/349), respectively. The proportion of peripheral submicroscopic infections was higher in Benin (83%) than in Mozambique (60%) and Gabon (55%; P = 0.033). Past or chronic placental P. falciparum infection was associated with an increased risk of preterm birth in Mozambican newborns (OR = 7.05, 95% CI 1.79 to 27.82). Microscopic infections were associated with reductions in haemoglobin levels at delivery among Mozambican women (-1.17 g/dL, 95% CI -2.09 to -0.24) as well as with larger drops in haemoglobin levels from recruitment to delivery in Mozambican (-1.66 g/dL, 95% CI -2.68 to -0.64) and Gabonese (-0.91 g/dL, 95% CI -1.79 to -0.02) women. Doubling qPCR-peripheral parasite densities in Mozambican women were associated with decreases in haemoglobin levels at delivery (-0.16 g/dL, 95% CI -0.29 to -0.02) and increases in the drop of haemoglobin levels (-0.29 g/dL, 95% CI -0.44 to -0.14). Beninese women had higher anti-parasite IgGs than Mozambican women (P < 0.001). No difference was found in the proportion of submicroscopic infections nor in the adverse impact of P. falciparum infections in HIV-infected women from Kenya (P. falciparum prevalence by qPCR: 9%, 32/351) and Mozambique (4%, 15/417). CONCLUSIONS: The lowest levels of resistance and tolerance in pregnant women from areas of low malaria transmission were accompanied by the largest adverse impact of P. falciparum infections. Exposure-dependent mechanisms developed by pregnant women to resist the infection and minimise pathology can reduce malaria-related adverse outcomes. Distinguishing both types of defences is important to understand how reductions in transmission can affect malaria disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00811421 . Registered 18 December 2008.
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Malaria Falciparum/transmisión , Complicaciones Infecciosas del Embarazo , Adulto , Parto Obstétrico , Femenino , Gabón , Infecciones por VIH/complicaciones , Humanos , Recién Nacido , Kenia , Malaria Falciparum/epidemiología , Microscopía , Mozambique , Parto , Placenta , Plasmodium falciparum/inmunología , Embarazo , Resultado del Embarazo , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Adulto JovenRESUMEN
OBJECTIVES: The objective of this study was to inform public health actions to limit first-line ART failure and HIV drug resistance in Mozambique. METHODS: This was a cross-sectional study. HIV-1-infected adults on first-line ART for at least 1 year attending routine visits in the Manhiça District Hospital, in a semi-rural area in southern Mozambique with no HIV-1 RNA monitoring available, were evaluated for clinical, socio-demographic, therapeutic, immunological and virological characteristics. Factors associated with HIV-1 RNA ≥1000 copies/mL and HIV drug resistance were determined using multivariate logistic regression. RESULTS: The study included 334 adults on first-line ART for a median of 3 years, of which 65% (214/332) had suppressed viraemia, 11% (37/332) had low-level viraemia (HIV-1 RNA 150-999 copies/mL) and 24% (81/332) had overt virological failure (HIV-1 RNA ≥1000 copies/mL). HIV drug resistance was detected in 89% of subjects with virological failure, but in none with low-level viraemia. Younger age [ORâ=â0.97 per additional year (95% CIâ=â0.94-1.00), Pâ=â0.039], ART initiation at WHO stage III/IV [ORâ=â2.10 (95% CIâ=â1.23-3.57), Pâ=â0.003] and low ART adherence [ORâ=â2.69 (95% CIâ=â1.39-5.19), Pâ=â0.003] were associated with virological failure. Longer time on ART [ORâ=â1.55 per additional year (95% CIâ=â1.00-2.43), Pâ=â0.052] and illiteracy [ORâ=â0.24 (95% CIâ=â0.07-0.89), Pâ=â0.033] were associated with HIV drug resistance. Compared with HIV-1 RNA, clinician's judgement of ART failure, based on clinical and immunological outcomes, only achieved 29% sensitivity and misdiagnosed 1 out of every 4.5 subjects. CONCLUSIONS: Public health programmes in Mozambique should focus on early HIV diagnosis, early ART initiation and adherence support. Virological monitoring drastically improves the diagnosis of ART failure, enabling a better use of resources.
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Antirretrovirales/uso terapéutico , Farmacorresistencia Viral , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/genética , Adulto , Estudios Transversales , Monitoreo de Drogas , Femenino , Técnicas de Genotipaje , VIH-1/clasificación , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Mozambique , Población Suburbana , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). METHODS AND FINDINGS: A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. CONCLUSIONS: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.
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Antimaláricos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Malaria/prevención & control , Mefloquina/administración & dosificación , Complicaciones Infecciosas del Embarazo/prevención & control , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Adulto , Método Doble Ciego , Femenino , Estudios de Seguimiento , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Kenia/epidemiología , Malaria/diagnóstico , Malaria/epidemiología , Mozambique/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Parasitarias del Embarazo/diagnóstico , Complicaciones Parasitarias del Embarazo/epidemiología , Complicaciones Parasitarias del Embarazo/prevención & control , Resultado del Embarazo , Tanzanía/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The effectiveness of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is threatened by increasing SP-resistance in Africa. We assessed the level of SP-resistance markers, and the clinical and parasitological effectiveness of IPTp-SP in southern Mozambique. METHODS: P. falciparum infection, antimalarial antibodies and dhfr/dhps SP-resistance mutants were detected by quantitative polymerase chain reaction (qPCR), suspension array technology and targeted deep sequencing, respectively, among 4016 HIV-negative women in Maputo province (2016-2019). Univariate and multivariate regression models were used to assess the association between taking the recommended three or more IPTp-SP doses (IPTp3+) and parasitological and clinical outcomes. RESULTS: 84.3% (3385/4016) women received three or more IPTp-SP doses. The prevalence of quintuple mutants at first antenatal care (ANC) visit was 94.2%. IPTp3+ was associated with a higher clearance rate of qPCR-detected infections from first ANC visit to delivery (adjusted odds ratio [aOR]=5.9, 95% CI: 1.5-33.3; p = 0.012), lower seroprevalence at delivery of antibodies against the pregnancy-specific antigen VAR2CSADBL34 (aOR=0.72, 95% CI: 0.54-0.95; p = 0.022), and lower prevalence of low birth weight deliveries (aOR: 0.61, 95% CI: 0.41-0.90; p = 0.013). CONCLUSION: A sustained parasitological effect of IPTp-SP contributes to the clinical effectiveness of IPTp3+ in areas with high prevalence of SP-resistance markers.
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Antimaláricos , Combinación de Medicamentos , Resistencia a Medicamentos , Malaria Falciparum , Plasmodium falciparum , Pirimetamina , Sulfadoxina , Humanos , Femenino , Sulfadoxina/uso terapéutico , Sulfadoxina/administración & dosificación , Pirimetamina/uso terapéutico , Pirimetamina/administración & dosificación , Embarazo , Antimaláricos/uso terapéutico , Adulto , Malaria Falciparum/prevención & control , Malaria Falciparum/epidemiología , Plasmodium falciparum/efectos de los fármacos , Plasmodium falciparum/genética , Mozambique/epidemiología , Adulto Joven , Complicaciones Parasitarias del Embarazo/prevención & control , Complicaciones Parasitarias del Embarazo/tratamiento farmacológico , Adolescente , Quimioprevención/métodosRESUMEN
Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, are consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declines in both populations (p = 0.002-0.007), while for the ANC population, population genetic diversity is also lower (p = 0.0004), and genetic relatedness between infections is higher (p = 0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.
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Malaria Falciparum , Malaria , Parásitos , Niño , Animales , Femenino , Embarazo , Humanos , Atención Prenatal/métodos , Mozambique/epidemiología , Malaria/epidemiología , Malaria/prevención & control , Plasmodium falciparum/genética , Genómica , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Malaria Falciparum/parasitologíaRESUMEN
Pregnant women attending first antenatal care (ANC) visits represent a promising malaria surveillance target in Sub-Saharan Africa. We assessed the spatio-temporal relationship between malaria trends at ANC (n = 6471) and in children in the community (n = 3933) and at health facilities (n = 15,467) in southern Mozambique (2016-2019). ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status (Pearson correlation coefficient [PCC] > 0.8, χ²<1.1), with a 2-3 months lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, did multigravidae show lower rates than children (PCC = 0.61, 95%CI[-0.12-0.94]). Seroprevalence against the pregnancy-specific antigen VAR2CSA reflected declining malaria trends (PCC = 0.74, 95%CI[0.24-0.77]). 60% (9/15) of hotspots detected from health facility data (n = 6662) using a novel hotspot detector, EpiFRIenDs, were also identified with ANC data (n = 3616). Taken together, we show that ANC-based malaria surveillance offers contemporary information on temporal trends and geographic distribution of malaria burden in the community.
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Malaria , Atención Prenatal , Niño , Embarazo , Femenino , Humanos , Estudios Seroepidemiológicos , Malaria/diagnóstico , Malaria/epidemiología , Instituciones de Salud , Mozambique/epidemiologíaRESUMEN
Pregnant women attending first antenatal care (ANC) visits represent a promising malaria surveillance target in Sub-Saharan Africa. Here we assessed the spatio-temporal relationship between malaria at ANC (n=6,471), in children at the community(n=9,362) and at health facilities (n=15,467) in southern Mozambique (2016-2019). ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status (Pearson correlation coefficient [PCC]>0.8, χ²<1.1), with a 2-3 months lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, multigravidae showed lower rates than children (PCC=0.61, 95%CI[-0.12-0.94]). Seroprevalence against the pregnancy-specific antigen VAR2CSA reflected declining malaria trends (PCC=0.74, 95%CI[0.24-0.77]). 80% (12/15) of hotspots detected from health facility data using a novel hotspot detector, EpiFRIenDs, were also identified with ANC data. The results show that ANC-based malaria surveillance offers contemporary information on temporal trends and the geographic distribution of malaria burden in the community.
RESUMEN
Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compared the genetic structure of parasite populations sampled from 289 first ANC attendees and 93 children from the community in Mozambique between 2015 and 2019. Samples were amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, were consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declined in both populations (p=0.002-0.007), while for the ANC population, population genetic diversity was also lower (p=0.0004), and genetic relatedness between infections were higher (p=0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.
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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, 32â138 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 30â163]) 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.
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Anemia , Malaria Cerebral , Síndrome de Dificultad Respiratoria , Adolescente , Niño , Preescolar , Hospitales de Distrito , Humanos , Lactante , Mozambique/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: There are 170,000 children living with HIV in 2017 in Mozambique. Scaling-up HIV care requires effective retention along the cascade. We sought to evaluate the pediatric cascade in HIV care at the Manhiça District Hospital. METHODS: A prospective cohort of children <15 years was followed from enrollment in HIV care (January 2013 to December 2015) until December 2016. Loss to follow-up (LTFU) was defined as not attending the HIV hospital visits for ≥90 days following last visit attended. RESULTS: From the 438 children included {median age at enrollment in care of 3,6 [interquartile range (IQR): 1.1-8.6] years}, 335 (76%) were antiretroviral therapy (ART) eligible and among those, 263 (78%) started ART at enrollment in HIV care. A total of 362 children initiated ART during the study period and the incidence rate of LTFU at 12, 24, and 36 months post-ART initiation was 41 [95% confidence interval (CI): 34-50], 34 (95% CI: 29-41), and 31 (95% CI: 27-37) per 100 children-years, respectively. Median time to LTFU was 5.8 (IQR: 1.4-12.7) months. Children 5-9 years of age had a lower risk of LTFU compared with children <1 year [adjusted subhazard ratio 0.36 (95% CI: 0.20-0.61)]. Re-engagement in care (RIC) was observed in 25% of the LTFU children. CONCLUSIONS: The high LTFU found in this study highlights the special attention that should be given to younger children during the first 6 months post-ART initiation to prevent LTFU. Once LTFU, only a quarter of those children return to the health unit. Elucidating factors associated with RIC could help to fine tune interventions which promote RIC.
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Fármacos Anti-VIH/uso terapéutico , Servicios de Salud Comunitaria , Infecciones por VIH/tratamiento farmacológico , Recuento de Linfocito CD4 , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Perdida de Seguimiento , Masculino , Mozambique , Estudios Prospectivos , Investigación Cualitativa , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: Few data on HIV resistance in pregnancy are available from Mozambique, one of the countries with the highest HIV toll worldwide. Understanding the patterns of HIV drug resistance in pregnant women might help in tailoring optimal regimens for prevention of mother to child transmission of HIV (pMTCT) and antenatal care. OBJECTIVES: To describe the frequency and characteristics of HIV drug resistance mutations (HIVDRM) in pregnant women with virological failure at delivery, despite pMTCT or antiretroviral therapy (ART). METHODS: Samples from HIV-infected pregnant women from a rural area in southern Mozambique were analysed. Only women with HIV-1 RNA >400c/mL at delivery were included in the analysis. HIVDRM were determined using MiSeq® (detection threshold 1%) at the first antenatal care (ANC) visit and at the time of delivery. RESULTS: Ninety and 60 samples were available at the first ANC visit and delivery, respectively. At first ANC, 97% of the women had HIV-1 RNA>400c/mL, 39% had CD4+ counts <350 c/mm3 and 30% were previously not on ART. Thirteen women (14%) had at least one HIVDRM of whom 70% were not on previous ART. Eight women (13%) had at least one HIVDRM at delivery. Out of 37 women with data available from the two time points, 8 (21%) developed at least one new HIVDRM during pMTCT or ART. Twenty seven per cent (53/191), 32% (44/138) and 100% (5/5) of the mutations that were present at enrolment, delivery and that emerged during pregnancy, respectively, were minority mutations (frequency <20%). CONCLUSIONS: Even with ultrasensitive HIV-1 genotyping, less than 20% of women with detectable viremia at delivery had HIVDRM before initiating pMTCT or ART. This suggests that factors other than pre-existing resistance, such as lack of adherence or interruptions of the ANC chain, are also relevant to explain lack of virological suppression at the time of delivery in women receiving antiretrovirals drugs during pregnancy.
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Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Recuento de Linfocito CD4/métodos , Femenino , VIH-1/efectos de los fármacos , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Mozambique , Embarazo , Atención Prenatal/métodos , Adulto JovenRESUMEN
BACKGROUND: In low-income countries, data on prevalence and effects of group B Streptococcus (GBS) and Escherichia coli (E. coli) colonization among pregnant women are scarce, but necessary to formulate prevention strategies. We assessed prevalence of GBS and E. coli colonization and factors associated among pregnant women, its effect in newborns and acceptability regarding the utilized sampling methods in a semirural Mozambican hospital. METHODS: Pregnant women were recruited from June 2014 to January 2015, during routine antenatal clinics at gestational age ≥ 34 weeks (n = 200); or upon delivery (n = 120). Maternal risk factors were collected. Vaginal and vagino-rectal samples for GBS and E. coli determination were obtained and characterized in terms of antimicrobial resistance and serotype. Anti-GBS antibodies were also determined. Neonatal follow-up was performed in the first 3 months after birth. Semistructured interviews were performed to investigate acceptability of sample collection methods. RESULTS: In total, 21.3% of women recruited were GBS carriers, while 16.3% were positive for E. coli. Prevalence of HIV was 36.6%. No association was found between being colonized by GBS and E. coli and maternal risk factors. GBS isolates were fully susceptible to penicillin and ampicillin. Serotypes V (32.4%), Ia (14.7%) and III (10.3%) were the most commonly found and 69.2% of the women tested had immunoglobuline G antibodies against GBS. E. coli isolates showed resistance to ampicillin in 28.9% and trimethoprim/sulfamethoxazole in 61.3% of the cases. CONCLUSION: Prevalence of GBS and/or E. coli colonization among pregnant women is high in this semirural community and comparable with those reported in similar settings. Four serotypes accounted for nearly 70% of all isolates of GBS. Population-based data on infant GBS infections would enable the design of prevention strategies for GBS disease in Mozambique.
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Portador Sano/epidemiología , Escherichia coli/aislamiento & purificación , Madres , Streptococcus agalactiae/aislamiento & purificación , Adulto , Portador Sano/microbiología , Infecciones por Escherichia coli/epidemiología , Femenino , Hospitales de Distrito , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Mozambique/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Prevalencia , Estudios Prospectivos , Recto/microbiología , Factores de Riesgo , Infecciones Estreptocócicas/epidemiología , Vagina/microbiología , Adulto JovenRESUMEN
BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity. METHODS: A cross sectional study was conducted among pregnant mothers attending Manhiça District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology. RESULTS: From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p<0.001. No differences on cCMV prevalence were found among HIV-exposed and unexposed. All (100%) mothers were seropositive for CMV IgG. RT-PCR of EV and B19V in DUC were both negative in all screened cases. No histological specific findings were found in placental tissues. No risk factors associated to vertical transmission of these viral infections were found. CONCLUSIONS: This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings.
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Infecciones por Citomegalovirus , Infecciones por Enterovirus , Eritema Infeccioso , Transmisión Vertical de Enfermedad Infecciosa , Estudios Transversales , Infecciones por Citomegalovirus/congénito , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/transmisión , Infecciones por Enterovirus/sangre , Infecciones por Enterovirus/congénito , Infecciones por Enterovirus/epidemiología , Infecciones por Enterovirus/transmisión , Eritema Infeccioso/sangre , Eritema Infeccioso/congénito , Eritema Infeccioso/epidemiología , Eritema Infeccioso/transmisión , Femenino , Humanos , Recién Nacido , Masculino , Mozambique , Proyectos Piloto , ARN Viral/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To assess morbidity and mortality in HIV-exposed uninfected (HEU) children to help guiding appropriate clinical care and effective preventive interventions. DESIGN: This is a longitudinal study comparing two cohorts of children; one born to HIV-infected women and the other born to HIV-uninfected women. METHODS: We have analyzed prospectively obtained information on nutritional status, morbidity and mortality from 966 HEU and 909 HIV-unexposed infants followed up until their first 18 months of life at a referral health facility in southern Mozambique. Determinants for adverse health outcomes in HEU children were also assessed using multivariate logistic regression. RESULTS: Increased incidence of hospital admissions (Pâ=â0.0015), shorter survival in the first 18 months of life (Pâ=â0.0510) and moderate and severe malnutrition (Pâ=â0.0006 and 0.0014, respectively) were observed among HEU children compared with HIV-unexposed children. Incidence of outpatient attendance in HEU children was associated with being men, older age and the mother being on antiretroviral treatment. Among HEU children, those who were never breastfed, or who were weaned or were partially breastfed, had an increased incidence of hospital admissions compared with children who were exclusively breastfed. CONCLUSION: Maternal HIV infection has important health consequences in non-HIV-infected children. As the prevalence of HIV-infected pregnant women is maintained and the proportion of HIV-infected children declines because of the scale-up of antiretroviral treatment during pregnancy and breastfeeding, more focus should be given to the health needs of HEU children to ensure that the post-2015 sustainable development goals are met.