Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial.

BACKGROUND: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria. METHODS: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries. Patients had microscopically-confirmed uncomplicated P falciparum malaria (>1000 and <150 000 parasites per µL). Part A identified the optimal dose regimens in adults and adolescents (aged ≥12 years) and in part B, the selected doses were assessed in children (≥2 years and <12 years). In part A, patients were randomly assigned to one of seven groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days; ganaplacide 800 mg plus lumefantrine-SDF 960 mg as a single dose; once a day ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; once a day ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; or twice a day artemether plus lumefantrine for 3 days [control]), with stratification by country (2:2:2:2:2:2:1) using randomisation blocks of 13. In part B, patients were randomly assigned to one of four groups (once a day ganaplacide 400 mg plus lumefantrine-SDF 960 mg for 1, 2, or 3 days, or twice a day artemether plus lumefantrine for 3 days) with stratification by country and age (2 to <6 years and 6 to <12 years; 2:2:2:1) using randomisation blocks of seven. The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29, analysed in the per protocol set. The null hypothesis was that the response was 80% or lower, rejected when the lower limit of two-sided 95% CI was higher than 80%. This study is registered with EudraCT (2020-003284-25) and ClinicalTrials.gov (NCT03167242). FINDINGS: Between Aug 2, 2017, and May 17, 2021, 1220 patients were screened and of those, 12 were included in the run-in cohort, 337 in part A, and 175 in part B. In part A, 337 adult or adolescent patients were randomly assigned, 326 completed the study, and 305 were included in the per protocol set. The lower limit of the 95% CI for PCR-corrected adequate clinical and parasitological response on day 29 was more than 80% for all treatment regimens in part A (46 of 50 patients [92%, 95% CI 81-98] with 1 day, 47 of 48 [98%, 89-100] with 2 days, and 42 of 43 [98%, 88-100] with 3 days of ganaplacide 400 mg plus lumefantrine-SDF 960 mg; 45 of 48 [94%, 83-99] with ganaplacide 800 mg plus lumefantrine-SDF 960 mg for 1 day; 47 of 47 [100%, 93-100] with ganaplacide 200 mg plus lumefantrine-SDF 480 mg for 3 days; 44 of 44 [100%, 92-100] with ganaplacide 400 mg plus lumefantrine-SDF 480 mg for 3 days; and 25 of 25 [100%, 86-100] with artemether plus lumefantrine). In part B, 351 children were screened, 175 randomly assigned (ganaplacide 400 mg plus lumefantrine-SDF 960 mg once a day for 1, 2, or 3 days), and 171 completed the study. Only the 3-day regimen met the prespecified primary endpoint in paediatric patients (38 of 40 patients [95%, 95% CI 83-99] vs 21 of 22 [96%, 77-100] with artemether plus lumefantrine). The most common adverse events were headache (in seven [14%] of 51 to 15 [28%] of 54 in the ganaplacide plus lumefantrine-SDF groups and five [19%] of 27 in the artemether plus lumefantrine group) in part A, and malaria (in 12 [27%] of 45 to 23 [44%] of 52 in the ganaplacide plus lumefantrine-SDF groups and 12 [50%] of 24 in the artemether plus lumefantrine group) in part B. No patients died during the study. INTERPRETATION: Ganaplacide plus lumefantrine-SDF was effective and well tolerated in patients, especially adults and adolescents, with uncomplicated P falciparum malaria. Ganaplacide 400 mg plus lumefantrine-SDF 960 mg once daily for 3 days was identified as the optimal treatment regimen for adults, adolescents, and children. This combination is being evaluated further in a phase 2 trial (NCT04546633). FUNDING: Novartis and Medicines for Malaria Venture.

Mapping of schistosomiasis and soil-transmitted helminthiases across 15 provinces of Angola.

INTRODUCTION: Schistosomiasis (SCH) and soil transmitted helminthiases (STH) have been historically recognized as a major public health problem in Angola. However, lack of reliable, country wide prevalence data on these diseases has been a major hurdle to plan and implement programme actions to target these diseases. This study aimed to characterize SCH and STH prevalence and distribution in Angola. METHODS: A country wide mapping was conducted in October 2018 (1 province) and from July to December 2019 (14 provinces) in school aged (SAC) children in 15 (of 18) provinces in Angola, using WHO protocols and procedures. A total of 640 schools and an average of 50 students per school (N = 31,938 children) were sampled. Stool and urine samples were collected and processed using the Kato-Katz method and Urine Filtration. Prevalence estimates for SCH and STH infections were calculated for each province and district with 95% confidence intervals. Factors associated with SCH and STH infection, respectively, were explored using multivariable logistic regression accounting for clustering by school. RESULTS: Of the 131 districts surveyed, 112 (85.5%) are endemic for STH, 30 (22.9%) have a prevalence above 50%, 24 (18.3%) are at moderate risk (prevalence 20%-50%), and 58 (44.3%) are at low risk (<20% prevalence); similarly, 118 (90,1%) of surveyed districts are endemic for any SCH, 2 (1.5%) are at high risk (>50% prevalence), 59 (45.0%) are at moderate risk (10%-50% prevalence), and 57 (43.5%) are at low risk (<10% prevalence). There were higher STH infection rates in the northern provinces of Malanje and Lunda Norte, and higher SCH infection rates in the southern provinces of Benguela and Huila. CONCLUSIONS: This mapping exercise provides essential information to Ministry of Health in Angola to accurately plan and implement SCH and STH control activities in the upcoming years. Data also provides a useful baseline contribution for Angola to track its progress towards the 2030 NTD roadmap targets set by WHO.

Annual home-based HIV testing in the Chókwè Health Demographic Surveillance System, Mozambique, 2014 to 2019: serial population-based survey evaluation.

INTRODUCTION: WHO recommends implementing a mix of community and facility testing strategies to diagnose 95% of persons living with HIV (PLHIV). In Mozambique, a country with an estimated 506,000 undiagnosed PLHIV, use of home-based HIV testing services (HBHTS) to help achieve the 95% target has not been evaluated. METHODS: HBHTS was provided at 20,000 households in the Chókwè Health Demographic Surveillance System (CHDSS), Mozambique, in annual rounds (R) during 2014 to 2019. Trends in prevalence of HIV infection, prior HIV diagnosis among PLHIV (diagnostic coverage), and undiagnosed HIV infection were assessed with three population-based surveys conducted in R1 (04/2014 to 04/2015), R3 (03/2016 to 12/2016), and R5 (04/2018 to 03/2019) of residents aged 15 to 59 years. Counts of patients aged ≥15 years tested for HIV in CHDSS healthcare facilities were obtained from routine reports. RESULTS: During 2014 to 2019, counsellors conducted 92,512 home-based HIV tests and newly diagnosed 3711 residents aged 15 to 59 years. Prevalence of HIV infection was stable (R1, 25.1%; R3 23.6%; R5 22.9%; p-value, 0.19). After the first two rounds (44,825 home-based tests; 31,717 facility-based tests), diagnostic coverage increased from 73.8% (95% CI 70.3 to 77.2) in R1 to 93.0% (95% CI 91.3 to 94.7) in R3, and prevalence of undiagnosed HIV infection decreased from 6.6% (95% CI 5.6 to 7.5) in R1 to 1.7% (95% CI 1.2 to 2.1) in R3. After two more rounds (32,226 home-based tests; 46,003 facility-based tests), diagnostic coverage was 95.4% (95% CI 93.7 to 97.1) and prevalence of undiagnosed HIV infection was 1.1% (95% CI 0.7 to 1.5) in R5. Prevalence of having last tested at home was 12.7% (95% CI 11.3 to 14.0) in R1, 45.2% (95% CI 43.4 to 47.0) in R3, and 41.4% (95% CI 39.5 to 43.2) in R5, and prevalence of having last tested at a healthcare facility was 45.3% (95% CI 43.3 to 47.3) in R1, 40.1% (95% CI 38.4 to 41.8) in R3, and 45.2% (95% CI 43.3 to 47.0) in R5. CONCLUSIONS: HBHTS successfully augmented facility-based testing to achieve HIV diagnostic coverage in a high-burden community of Mozambique. HBHTS should be considered in sub-Saharan Africa communities striving to diagnose 95% of persons living with HIV.

Prevalence of Voluntary Medical Male Circumcision for HIV Infection Prevention - Chókwè District, Mozambique, 2014-2019.

Male circumcision is an important preventive strategy that confers lifelong partial protection (approximately 60% reduced risk) against heterosexually acquired HIV infection among males (1). In Mozambique, the prevalence of male circumcision was 51% when the voluntary medical male circumcision (VMMC) program began in 2009. The Mozambique Ministry of Health set a goal of 80% circumcision prevalence among males aged 10-49 years by 2019 (2). CDC analyzed data from five cross-sectional surveys of the Chókwè Health and Demographic Surveillance System (CHDSS) to evaluate progress toward the goal and guide ongoing needs for VMMC in Mozambique. During 2014-2019, circumcision prevalence among males aged 15-59 years increased 42%, from 50.1% to 73.5% (adjusted prevalence ratio [aPR] = 1.42). By 2019, circumcision prevalence among males aged 15-24 years was 90.2%, exceeding the national goal (2). However, circumcision prevalence among males in older age groups remained below 80%; prevalence was 62.7%, 54.5%, and 55.7% among males aged 25-34, 35-44, and 45-59 years, respectively. A multifaceted strategy addressing concerns about the safety of the procedure, cultural norms, and competing priorities that lead to lack of time could help overcome barriers to circumcision among males aged ≥25 years.

High Coverage of Antiretroviral Treatment With Annual Home-Based HIV Testing, Follow-up Linkage Services, and Implementation of Test and Start: Findings From the Chókwè Health Demographic Surveillance System, Mozambique, 2014-2019.

BACKGROUND: Early antiretroviral therapy (ART) is necessary for HIV epidemic control and depends on early diagnosis and successful linkage to care. Since 2014, annual household-based HIV testing and counseling and linkage services have been provided through the Chókwè Health and Demographic Surveillance System for residents testing HIV positive in this high HIV-burden district. METHODS: District-wide Test and Start [T&S, ART for all people living with HIV (PLHIV)] began in August 2016, supported by systematic interventions to improve linkage to care and treatment. Annual rounds (R) of random household surveys were conducted to assess trends in population prevalence of ART use and viral load suppression (<1000 viral RNA copies/mL). RESULTS: Between R1 (April 2014-April 2015) and R5 (April 2018-Mar 2019), 46,090 (67.2%) of 68,620 residents aged 15-59 years were tested for HIV at home at least once, and 3711 were newly diagnosed with HIV and provided linkage services. Population prevalence of current ART use among PLHIV increased from 65.0% to 87.5% between R1 and R5. ART population prevalence was lowest among men aged 25-34 years (67.8%) and women aged 15-24 (78.0%), and highest among women aged 35-44 years (93.6%) and 45-59 years (93.7%) in R5. Viral load suppression prevalence increased among all PLHIV aged 15-59 years from 52.0% in R1 to 78.3% in R5. DISCUSSION: Between 2014 and 2019, Chókwè Health and Demographic Surveillance System residents surpassed the UNAIDS targets of ≥81% of PLHIV on ART and ≥73% virally suppressed. This achievement supports the combination of efforts from household-based HIV testing and counseling, support for linkage to care and treatment, and continued investments in T&S implementation.

Two-Stage anaerobic digestion in agroindustrial waste treatment: A review.

The anaerobic digestion is a process widely recognized as an interesting alternative for the treatment and stabilization of residual organic substrates. However, several technical limitations were observed based on the characteristics of the organic matter submitted to the process, such as the presence of high concentrations of soluble sugars or fats. The technology of anaerobic digestion in multiple stages is described as a viable option in the control of variables, optimizing the environmental conditions of the main microorganisms involved in the process, assuring high solid removal and methane production, besides allowing a higher energy yield through the generation of molecular fuel hydrogen. Several studies reviewed the process of anaerobic digestion in multiple stages in the treatment of food waste, although few report its use applied directly to agroindustrial residues. Thus, the present work aims to review the literature evaluating the scenario and viability of the multi-stage anaerobic digestion process applied to agroindustrial effluents. Effluents such as manipueira, vinasse, and dairy wastewater are substrates that present high yields when treated by AD processes with stage separation. The high concentration of easily fermentable sugars results in a high production of molecular hydrogen (co-product of the production of volatile acids in the acid phase) and methane (methanogenic phase). The great challenges related to the development of the sector are focused on the stability of the composition and yield of hydrogen in the acid phase, besides the problems resulting from the treatment of complex residues. Thus, the present study suggests that future works should focus on the technologies of new microorganisms and optimization of process parameters, providing maturation and scale-up of the two-stage anaerobic digestion technique.

Use of rice husk in waste cooking oil pretreatment.

Since industrial wastes are increasing, the development of studies to find ways for their use is urgent. Waste cooking oil is an important source for the production of biodiesel, one of the main biofuels in Brazil. However, during cooking, the oil undergoes conditions that change its properties and decrease its quality, such as its acidity value. Current research treats waste cooking oil by the adsorption process using rice husk, an agro-industrial waste, and activated carbon to compare results. The potential of the adsorbents to remove free fatty acids in waste cooking oil has been investigated by the batch technique, evaluating different operating conditions of temperature, adsorbent mass and agitation. Adsorbents were characterized by nitrogen physisorption, scanning electron microscope, energy-dispersive spectroscopy and X-ray diffraction. The maximum result obtained for activated carbon at acidity reduction was 63%, using 22.4°C, 169.64 rpm and 3.39 g of adsorbent mass. Already, using the rice husk the percentage of removal was the same, 63% using 22.4°C, 80.36 rpm and 1.61 g of adsorbent, however in shorter times. The results prove that the application of the rice husk for this purpose is advantageous, for being a low-cost material, available on a large scale and that provide results similar to activated carbon.

Low and Decreasing Prevalence and Rate of False Positive HIV Diagnosis - Chókwè District, Mozambique, 2014-2017.

In 2017, rapid human immunodeficiency virus (HIV) testing services enabled the HIV diagnosis and treatment of approximately 15.3 million persons with HIV infection in sub-Saharan Africa with life-saving antiretroviral therapy (ART) (1). Although suboptimal testing practices and misdiagnoses have been reported in sub-Saharan Africa and elsewhere, trends in population burden and rate of false positive HIV diagnosis (false diagnosis) have not been reported (2,3). Understanding the population prevalence and trends of false diagnosis is fundamental for guiding rapid HIV testing policies and practices. To help address this need, CDC analyzed data from 57,655 residents aged 15-59 years in the Chókwè Health and Demographic Surveillance System (CHDSS) in Mozambique to evaluate trends in the rate (the percentage of false diagnoses among retested persons reporting a prior HIV diagnosis) and population prevalence of false diagnosis. From 2014 to 2017, the observed rate of false diagnosis in CHDSS decreased from 0.66% to 0.00% (p<0.001), and the estimated population prevalence of false diagnosis decreased from 0.08% to 0.01% (p = 0.0016). Although the prevalence and rate of false diagnosis are low and have decreased significantly in CHDSS, observed false diagnoses underscore the importance of routine HIV retesting before ART initiation and implementation of comprehensive rapid HIV test quality management systems (2,4,5).

Assessment of Efficacy and Safety of Arterolane Maleate-Piperaquine Phosphate Dispersible Tablets in Comparison With Artemether-Lumefantrine Dispersible Tablets in Pediatric Patients With Acute Uncomplicated Plasmodium falciparum Malaria: A Phase 3, Randomized, Multicenter Trial in India and Africa.

BACKGROUND: Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children. METHODS: This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days. RESULTS: The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar. CONCLUSIONS: The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients. CLINICAL TRIALS REGISTRATION: CTRI/2014/07/004764.

Tetanus Immunity Gaps in Children 5-14 Years and Men ≥ 15 Years of Age Revealed by Integrated Disease Serosurveillance in Kenya, Tanzania, and Mozambique.

Recent tetanus cases associated with male circumcision in Eastern and Southern Africa (ESA) prompted an examination of tetanus immunity by age and sex using multiplex serologic data from community surveys in three ESA countries during 2012-2013. Tetanus seroprotection was lower among children 5-14 years versus 1-4 years of age in Kenya (66% versus 90%) and Tanzania (66% versus 89%), but not in Mozambique (91% versus 88%), where children receive two booster doses in school. Among males ≥ 15 years of age, tetanus seroprotection was lower than females in Kenya (45% versus 96%), Tanzania (28% versus 94%), and Mozambique (64% versus 90%). Tetanus immunity from infant vaccination doses wanes over time, and only women of reproductive age routinely receive booster doses. To prevent immunity gaps in older children, adolescents, and adult men, a life-course vaccination strategy is needed to provide the three recommended tetanus booster doses.

Epidemiology of rotavirus A diarrhea in Chókwè, Southern Mozambique, from February to September, 2011.

Acute diarrhea disease caused by Rotaviruses A (RVA) is still the leading cause of morbidity and mortality in children ≤5 years old in developing countries. An exploratory cross-sectional study was conducted between February and September, 2011 to determine the proportion of acute diarrhea caused by RVA. A total of 254 stool specimens were collected from children ≤5 years old with acute diarrhea, including outpatients (222 children) and inpatients (32 children), in three local health centers in Chókwè District, Gaza Province, South of Mozambique. RVA antigens were detected using enzyme immunoassay (EIA); the RVA G (VP7) and P (VP4) genotypes were determined by RT-PCR or analysis sequencing. Sixty (24%) out of 254 fecal specimens were positive for RVA by EIA; being 58 (97%) from children ≤2 years of age. RVA prevalence peaks in June and July (coldest and drier months) and the G[P] binary combination observed were G12P[8] (57%); G1P[8] (9%); G12P[6] (6%); and 2% for each of the following genotypes: G1P[6], G2P[6] G4P[6], and G9P[8]. Non-Typeable (NT) G and/or P genotypes were observed as follows: G12P [NT] (6%); G1P [NT], G3P[NT] and GNTP[NT] (4%). Considering the different GP combinations, G12 represented 67% of the genotypes. This is the first data showing the diversity of RVA genotypes in Mozambique highlighting the epidemiological importance of these viruses in acute diarrhea cases in children ≤2 years old. In addition, these findings will provide a baseline data before the introduction of the RVA monovalent (Rotarix(®) ) vaccine in the National Immunization Program in September 2015. J. Med. Virol. 88:1751-1758, 2016. © 2016 Wiley Periodicals, Inc.

A Phase 3, Double-Blind, Randomized Study of Arterolane Maleate-Piperaquine Phosphate vs Artemether-Lumefantrine for Falciparum Malaria in Adolescent and Adult Patients in Asia and Africa.

BACKGROUND: Artemisinins, which are derived from plants, are subject to risk of supply interruption due to climatic changes. Consequently, an effort to identify a new synthetic antimalarial was initiated. A fixed-dose combination of arterolane maleate (AM), a new synthetic trioxolane, with piperaquine phosphate (PQP), a long half-life bisquinoline, was evaluated in patients with uncomplicatedPlasmodium falciparummalaria. METHODS: In this multicenter, randomized, double-blind, comparative, parallel-group trial, 1072 patients aged 12-65 years withP. falciparummonoinfection received either AM-PQP (714 patients) once daily or artemether-lumefantrine (A-L; 358 patients) twice daily for 3 days. All patients were followed up until day 42. RESULTS: Of the 714 patients in the AM-PQP group, 638 (89.4%) completed the study; of the 358 patients in the A-L group, 301(84.1%) completed the study. In both groups, the polymerase chain reaction corrected adequate clinical and parasitological response (PCR-corrected ACPR) on day 28 in intent-to-treat (ITT) and per-protocol (PP) populations was 92.86% and 92.46% and 99.25% and 99.07%, respectively. The corresponding figures on day 42 in the ITT and PP populations were 90.48% and 91.34%, respectively. After adjusting for survival ITT, the PCR-corrected ACPR on day 42 was >98% in both groups. The overall incidence of adverse events was comparable. CONCLUSIONS: AM-PQP showed comparable efficacy and safety to A-L in the treatment of uncomplicatedP. falciparummalaria in adolescent and adult patients. AM-PQP demonstrated high clinical and parasitological response rates as well as rapid parasite clearance. CLINICAL TRIALS REGISTRATION: India. CTRI/2009/091/000101.

HIV prevalence and incidence in a cohort of women at higher risk for HIV acquisition in Chókwè, southern Mozambique.

BACKGROUND: Reliable HIV incidence estimates for Mozambique are limited. We conducted a prospective HIV incidence study as part of a clinical research site development initiative in Chókwè district, Gaza Province, southern Mozambique. METHODS: Between June 2010 and October 2012, we recruited women at sites where women at higher risk of HIV infection would likely be found. We enrolled and tested 1,429 sexually active women in the screening phase and 479 uninfected women in the prospective phase. Participants were scheduled for 12+ months follow-up, when they underwent face-to-face interviews, HIV counseling and testing, and pregnancy testing. We observed a total of 373.1 woman-years (WY) of follow-up, with mean (median) of 9.4 (9.7) women-months per participant. RESULTS: The prevalence of HIV was 29.4% (95% confidence interval [CI]: 27.0-31.8%). In multivariable logistic regression analysis, factors that remained significantly associated with prevalent HIV were: older age (OR: 0.6; 95% CI: 0.4-0.7), lower educational level (OR: 0.4; 95% CI: 0.3-0.7), and using hormonal contraception (OR: 0.6; 95% CI: 0.4-0.7) or condoms (OR: 0.5; 95% CI: 0.3-0.7). We observed an HIV incidence rate of 4.6 per 100 WY (95% CI: 2.7, 7.3). The HIV incidence was 4.8 per 100 WY (95% CI: 2.5, 8.3) in women aged 18-24 years, 4.5 per 100 WY (95% CI: 1.2, 11.4) in women aged 25-29 years and 3.2 per 100 WY (95% CI: 0.1, 18.0) in the 30-35 years stratum. None of the demographic factors or time-varying behavioral factors examined was significantly associated with incident HIV infection in bivariable analysis at p ≤ 0.10. CONCLUSIONS: We found a high HIV incidence among sexually active young women in Chókwè, Mozambique. HIV prevention programs should be strengthened in the area, with more comprehensive reproductive health services, regular HIV testing, condom promotion, and messaging about multiple sexual partners.

HIV prevalence and incidence in a cohort of women at higher risk for HIV acquisition in Chókwè, southern Mozambique

Reliable HIV incidence estimates for Mozambique are limited. We conducted a prospective HIV incidence study as part of a clinical research site development initiative in Chókwè district, Gaza Province, southern Mozambique. Methods: Between June 2010 and October 2012, we recruited women at sites where women at higher risk of HIV infection would likely be found. We enrolled and tested 1,429 sexually active women in the screening phase and 479 uninfected women in the prospective phase. Participants were scheduled for 12+ months follow-up, when they underwent face-to-face interviews, HIV counseling and testing, and pregnancy testing. We observed a total of 373.1 woman-years (WY) of follow-up, with mean (median) of 9.4 (9.7) women-months per participant. Results: The prevalence of HIV was 29.4% (95% confidence interval [CI]: 27.0-31.8%). In multivariable logistic regression analysis, factors that remained significantly associated with prevalent HIV were: older age (OR: 0.6; 95% CI: 0.4-0.7), lower educational level (OR: 0.4; 95% CI: 0.3-0.7), and using hormonal contraception (OR: 0.6; 95% CI: 0.4-0.7) or condoms (OR: 0.5; 95% CI: 0.3-0.7). We observed an HIV incidence rate of 4.6 per 100 WY (95% CI: 2.7, 7.3). The HIV incidence was 4.8 per 100 WY (95% CI: 2.5, 8.3) in women aged 18-24 years, 4.5 per 100 WY (95% CI: 1.2, 11.4) in women aged 25-29 years and 3.2 per 100 WY (95% CI: 0.1, 18.0) in the 30-35 years stratum. None of the demographic factors or time-varying behavioral factors examined was significantly associated with incident HIV infection in bivariable analysis at p ≤ 0.10. Conclusions: We found a high HIV incidence among sexually active young women in Chókwè, Mozambique. HIV prevention programs should be strengthened in the area, with more comprehensive reproductive health services, regular HIV testing, condom promotion, and messaging about multiple sexual partners.

Frequencies of Cytochrome P450 2B6 and 2C8 Allelic Variants in the Mozambican Population.

BACKGROUND: The cytochrome P450 enzymes (CYP) play an important role in the metabolism of many therapeutic agents. The activities of different enzymes exhibit variability in different populations, which causes variations in drug response or toxicity. The CYP2B6 and CYP2C8 enzymes are encoded by polymorphic genes characterised by different single nucleotide polymorphisms (SNPs). Several of these CYP variants are often associated with slow metabolism phenotypes. This study aimed to analyse the frequencies of allelic variants of CYP2B6 and CYP2C8 in the Mozambican population. METHODS: Using a polymerase chain reaction and restriction fragment length polymorphism assay (PCR-RFLP), the frequencies of the allelic variants of CYP2B6 (c.64C>T, c.516G>T, c.777C>A, c.785A>G, c.1459C>T) and CYP2C8 (c.805A>T, c.416G>A, c.1196A>G, c.792C>G) were determined in 360 Mozambican blood donors. RESULTS: The frequencies of the allelic variants of the CYP2B6 gene were 0.057, 0.426, 0.0, 0.410, and 0.004. For the CYP2C8 gene, the frequencies of the allelic variants were 0.160, 0.048, 0.0, and 0.005. No significant differences were observed between the gender and geographic distribution of volunteers around the country. CONCLUSION: The frequencies of the allelic variants of the CYP2B6 and CYP2C8 genes were found to be homogeneously distributed in the Mozambican population and were comparable to other African populations. Further studies are required to explore the impact of these variants on the clinical response (efficacy and toxicity) of drugs, including antimalarials.

Dosis única de la vacuna oral de la cepa viva atenuada 638 de Vibrio cholerae essegura e inmunogénica en voluntarios adultos en Mozambique / A single dose of live-attenuated 638 Vibrio cholerae oral vaccine is safe and immunogenic in adult volunteers in Mozambique

Se realizó un ensayo clínico controlado con placebo, aleatorizado y a doble ciego, para evaluar la seguridad, reactogenicidad e inmunogenicidad del candidato vacunal liofilizado contra el cólera de la cepa viva atenuada 638 de V. cholerae O1 El Tor Ogawa. Se incluyeron 120 voluntarios de ambos sexos, aparentemente sanos, entre 18 y 50 años de edad, en Maputo, Mozambique, un área endémica de cólera, donde la seroprevalencia del virus de inmunodeficiencia humana (VIH) es de 20 por ciento a 30 por ciento. Ochenta sujetos recibieron como tratamiento una dosis oral de 2 x 10 9 UFC del candidato vacunal 638 y otros 40 una dosis del placebo que contenía solo los lioprotectores. Se realizó seguimiento ambulatorio de los eventos adversos durante 30 días. La respuesta inmune se evaluó por medio de la estimación de la tasa de seroconversión y la media geométrica del título (MGT) de anticuerpos vibriocidas en los sueros de los voluntaries, antes y a los 14 y 21 días posteriores a la inmunización. No se reportaron eventos adversos graves. La incidencia de eventos adversos reportados en el grupo que recibió la vacuna fue similar al del grupo placebo. Los eventos adversos encontrados fueron independientes de la detección de anticuerpos contra el VIH-1, VIH-2, hepatitis (H) A, HC y el antígeno de superficie del virus de la hepatitis B. La presencia de helmintos no modificó la incidencia de eventos adversos. La cepa vacunal fue aislada en 37 (46,25 por ciento) voluntarios que recibieron la vacuna. A los 14 días el pico de la MGT de anticuerpos vibriocidas en el grupo de la vacuna fue de 9056 frente a 39 en el grupo placebo, con una seroconversión total de 97,4 por ciento a los 21 días. Se concluye que el candidato vacunal 638 es seguro e inmunogénico en una región endémica de cólera(AU)

A placebo-controlled randomized, double-blind, clinical trial was carried out to assess the safety, reactogenicity,and immunogenicity of the lyophilized vaccine candidate against cholera derived from the live attenuated 638Vibrio cholerae O1 El Tor Ogawa strain. One hundred and twenty presumably healthy female and male adultvolunteers aged between 18 and 50 years were included. They were from Maputo, Mozambique a cholera endemicarea, where, in addition, human immunodeficiency virus (HIV) seroprevalence is from 20 to 30 percent A dose of 2 x 109 colony forming units (CFU) was given to 80 subjects and other 40 received only vaccine lyoprotectors as a placebocontrol. Out-patient follow-up of adverse events was carried out during the following 30 days after vaccination.The immune response was evaluated by the estimation of seroconversion rate and the geometric mean titer(GMT) of vibriocidal antibodies in the sera from volunteers that was collected previously, and at days 14 and 21after immunization. No serious adverse events were reported. The adverse events found in the vaccine groupwere similar to those of the placebo groups. They were independent from the detection of antibodies againstHIV-1, HIV-2, hepatitis (H) A; HC and hepatitis B surface antigen. The presence of helminthes did not modify the incidence of adverse events. The 638 vaccine strain was isolated in 37 (46,25 percent) vaccinated volunteers feces. The peak of the GMT of vibriocidal antibodies in the vaccine group was 9056 versus 39 in the placebo group at 14 dayswith a total seroconversion of 97,4 percent at 21 days. The 638 vaccine candidate is safe and immunogenic in a cholera endemic region(AU)

Preliminary report of HIV and Toxoplasma gondii occurrence in pregnant women from Mozambique / Descrição preliminar da ocorrência de infecção pelo HIV e toxoplasmose em mulheres grávidas em Moçambique

Toxoplasmosis, a protozoan disease, causes severe disease in fetuses during pregnancy and deadly encephalitis in HIV patients. There are several studies on its seroprevalence around the world, but studies focusing on African countries are limited in number and mostly anecdotal. We studied two groups of samples from Mozambique by ELISA, using serum samples from 150 pregnant women and six Cerebrospinal fluid (CSF) samples from AIDS patients with encephalitis. HIV status was confirmed, and CD4 blood counts were obtained from HIV-positive pregnant women. IgG seroprevalence of the group as a whole was 18.7 percent (28/150), with a higher prevalence in HIV-positive individuals compared to those who were HIV-negative (31.3 percent, [18/58] vs. 10.9 percent, [10/92]) patients. These data may be biased due to cumulative effects of exposition affecting disease prevalence. If corrected, this data may indicate an interaction of HIV and T. gondii. Prevalence of both diseases increases with age, but this is more clearly seen for toxoplasmosis (p < 0.005) than HIV infection, possibly explained by higher transmission of HIV after childhood. In HIV patients suffering from encephalitis, CSF serology showed that 33 percent of specific IgG CSF had a high avidity, which was in accordance with the data from the group of pregnant women. Lower prevalence rates of both infections in older groups could be explained by more deaths in the infected groups, resulting in an artificially lower prevalence. Using CD4 counts as a marker of time of HIV infection, and correcting for age, patients with contact with T. gondii had fewer CD4 cells, suggesting prolonged HIV disease or other causes. Toxoplasma IgG prevalence is higher in HIV+ groups, which could be ascribed to HIV- and T. gondii-associated risk factors, such as exposure to higher and more diverse social contacts. The low incidence of Toxoplasma IgG in younger age groups shows that transmission could be related to better access to cyst-containing meat in adulthood, as environmental transmission due to oocysts is usually blamed for higher incidence in children. Taken together, these data support the urgent need of research in toxoplasmosis in Africa, especially in the presence of HIV epidemics.

Toxoplasmose, uma protozoonose, causa doença grave em fetos de mulheres grávidas com infecção aguda e encefalite letal em portadores de HIV. Apesar de muitos estudos sobre sua prevalência no Mundo, existem apenas alguns relatos da toxoplasmose na África Austral, geralmente anedóticos. Estudamos por ELISA dois grupos de amostras de Moçambique, usando 150 amostras de soros de mulheres grávidas e seis amostras de Liquido Cefalorraquidiano (LCR) de pacientes com AIDS e encefalite. O estado da infecção pelo HIV foi confirmado e a contagem de células CD4+ no sangue foi obtida das pacientes grávidas infectadas pelo HIV. No grupo das gestantes, IgG anti T.gondii foi encontrada em 18.7 por cento (28/150), mais freqüente em pacientes HIV positivas (31.3 por cento, 18/58) do que em HIV negativas (10.9 por cento, 10/92). A ocorrência de ambas as doenças aumenta com a idade, mais claramente vista na toxoplasmose (p < 0.005) do que na infecção pelo HIV, devido maior transmissão do HIV após a infância. Na encefalite em pacientes HIV+, a sorologia do LCR mostrou uma ocorrência de 33 por cento de IgG especifica de alta avidez, que está de acordo com a ocorrência neste grupo etário, baseado nos dados de nossas gestantes. A menor ocorrência de ambas as infecções em grupos etários mais idosos pode ser explicada pela mortalidade cumulativa por qualquer causa nos grupos mais idosos, resultando em menor ocorrência relativa. Usando as contagens de células CD4+ como marcadores da progressão da infecção pelo HIV e corrigindo para grupos etários, as gestantes HIV+ com contato com T. gondii tem menores níveis de células CD4+ do que as gestantes HIV+ sem contato com T.gondii. A ocorrência maior da toxoplasmose em gestantes HIV+ pode ser atribuída a fatores de risco semelhantes, como exposição a maior contato social. A baixa ocorrência da toxoplasmose em grupos mais jovens pode se relacionar com menor acesso a carne contendo cistos, já que a transmissão ambiental por oocistos está associada à maior incidência em crianças. Todos estes dados reforçam a necessidade de pesquisa da toxoplasmose na África Austral, especialmente na presença da epidemia pelo HIV.

Efficacy and safety of a fixed-dose oral combination of pyronaridine-artesunate compared with artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria: a randomised non-inferiority trial.

BACKGROUND: There is a need for new artemisinin-based combination therapies that are convenient, effective, and safe. We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: This phase 3, parallel-group, double-blind, randomised, non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia. In a double-dummy design, patients aged 3-60 years with uncomplicated P falciparum malaria were randomly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day, orally for 3 days, plus respective placebo. Randomisation was done by computer-generated randomisation sequence in blocks of nine by study centre. Intervention tablets contained 180 mg pyronaridine and 60 mg artesunate; control tablets contained 20 mg artemether and 120 mg lumefantrine. Both treatments were given according to bodyweight. The primary efficacy outcome was PCR-corrected adequate clinical and parasitological response (ACPR) rate at day 28 in the per-protocol population. Non-inferiority was shown if the lower limit of the two-sided 95% CI for the difference between groups was greater than -5%. This study is registered with ClinicalTrials.gov, number NCT00422084. FINDINGS: 1272 patients were randomly assigned to treatment (pyronaridine-artesunate, n=849; artemether-lumefantrine, n=423). The per-protocol population consisted of 784 patients in the pyronaridine-artesunate group and 386 patients in the artemether-lumefantrine group. PCR-corrected ACPR rate at day 28 was 99.5% (780 patients; 95% CI 98.7-99.9) in the pyronaridine-artesunate group and 99.2% (383 patients; 95% CI 97.7-99.8) in the artemether-lumefantrine group (treatment difference 0.3%, 95% CI -0.7 to 1.8; p=0.578). There were 509 (60.0%) adverse events in 849 patients assigned to pyronaridine-artesunate and 241 (57.0%) in 423 patients assigned to artemether-lumefantrine. The most frequent drug-related adverse event was eosinophilia (pyronaridine-artesunate, 53 events [6.2%]; artemether-lumefantrine 24 events [5.7%]). 21 (2.5%) patients in the pyronaridine-artesunate group and seven (1.7%) in the artemether-lumefantrine group discontinued study drugs or were withdrawn from the study. Mild and transient increases in alanine aminotransferase and aspartate aminotransferase concentrations were seen in the pyronaridine-artesunate group but not in the artemether-lumefantrine group. INTERPRETATION: Efficacy of pyronaridine-artesunate was non-inferior to that of artemether-lumefantrine for treatment of uncomplicated falciparum malaria. Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes. FUNDING: Shin Poong Pharmaceutical and the Medicines for Malaria Venture.

Preliminary report of HIV and Toxoplasma gondii occurrence in pregnant women from Mozambique.

Toxoplasmosis, a protozoan disease, causes severe disease in fetuses during pregnancy and deadly encephalitis in HIV patients. There are several studies on its seroprevalence around the world, but studies focusing on African countries are limited in number and mostly anecdotal. We studied two groups of samples from Mozambique by ELISA, using serum samples from 150 pregnant women and six Cerebrospinal fluid (CSF) samples from AIDS patients with encephalitis. HIV status was confirmed, and CD4 blood counts were obtained from HIV-positive pregnant women. IgG seroprevalence of the group as a whole was 18.7% (28/150), with a higher prevalence in HIV-positive individuals compared to those who were HIV-negative (31.3%, [18/58] vs. 10.9%, [10/92]) patients. These data may be biased due to cumulative effects of exposition affecting disease prevalence. If corrected, this data may indicate an interaction of HIV and T. gondii. Prevalence of both diseases increases with age, but this is more clearly seen for toxoplasmosis (p < 0.005) than HIV infection, possibly explained by higher transmission of HIV after childhood. In HIV patients suffering from encephalitis, CSF serology showed that 33% of specific IgG CSF had a high avidity, which was in accordance with the data from the group of pregnant women. Lower prevalence rates of both infections in older groups could be explained by more deaths in the infected groups, resulting in an artificially lower prevalence. Using CD4 counts as a marker of time of HIV infection, and correcting for age, patients with contact with T. gondii had fewer CD4 cells, suggesting prolonged HIV disease or other causes. Toxoplasma IgG prevalence is higher in HIV+ groups, which could be ascribed to HIV- and T. gondii-associated risk factors, such as exposure to higher and more diverse social contacts. The low incidence of Toxoplasma IgG in younger age groups shows that transmission could be related to better access to cyst-containing meat in adulthood, as environmental transmission due to oocysts is usually blamed for higher incidence in children. Taken together, these data support the urgent need of research in toxoplasmosis in Africa, especially in the presence of HIV epidemics.

A 10 year study of the cause of death in children under 15 years in Manhiça, Mozambique.

BACKGROUND: Approximately 46 million of the estimated 60 million deaths that occur in the world each year take place in developing countries. Further, this mortality is highest in Sub-Saharan Africa, although causes of mortality in this region are not well documented. The objective of this study is to describe the most frequent causes of mortality in children under 15 years of age in the demographic surveillance area of the Manhiça Health Research Centre, between 1997 and 2006, using the verbal autopsy tool. METHODS: Verbal autopsy interviews for causes of death in children began in 1997. Each questionnaire was reviewed independently by three physicians with experience in tropical paediatrics, who assigned the cause of death according to the International Classification of Diseases (ICD-10). Each medical doctor attributed a minimum of one and a maximum of 2 causes. A final diagnosis is reached when at least two physicians agreed on the cause of death. RESULTS: From January 1997 to December 2006, 568,499 person-year at risk (pyrs) and 10,037 deaths were recorded in the Manhiça DSS. 3,730 deaths with 246,658 pyrs were recorded for children under 15 years of age. Verbal autopsy interviews were conducted on 3,002 (80.4%) of these deaths. 73.6% of deaths were attributed to communicable diseases, non-communicable diseases accounted for 9.5% of the defined causes of death, and injuries for 3.9% of causes of deaths. Malaria was the single largest cause, accounting for 21.8% of cases. Pneumonia with 9.8% was the second leading cause of death, followed by HIV/AIDS (8.3%) and diarrhoeal diseases with 8%. CONCLUSION: The results of this study stand out the big challenges that lie ahead in the fight against infectious diseases in the study area. The pattern of childhood mortality in Manhiça area is typical of developing countries where malaria, pneumonia and HIV/AIDS are important causes of death.