Orvalho Augusto

Incidence of Tuberculosis Among Young Children in Rural Mozambique

Background: Tuberculosis (TB) contributes significantly to child morbidity and mortality. This study aimed to estimate the minimum community-based incidence rate of TB among children <3 years of age in Southern Mozambique. Methods: Between October 2011 and October 2012, in the Manhiça District Health and Demographic Surveillance System, we enrolled prospectively all presumptive TB cases younger than 3 years of age through passive and active case finding. Participants included all children who were either symptomatic or were close contacts of a notified adult smear-positive pulmonary TB. Children were clinically evaluated at baseline and follow-up visits. Investigation for TB disease included chest radiography, HIV and tuberculin skin testing as well as gastric aspirate and induced sputum sampling, which were processed for smear, culture and mycobacterial molecular identification. Results: During the study period, 13,764 children <3 years contributed to a total of 9575 person-year. Out of the 789 presumptive TB cases enrolled, 13 had TB culture confirmation and 32 were probable TB cases. The minimum community-based incidence rate of TB (confirmed plus probable cases) was 470 of 100,000 person-year (95% confidence interval: 343–629 of 100,000). HIV co-infection was present in 44% of the TB cases. Conclusion: These data highlight the huge burden of pediatric TB. This study provides one of the first prospective population-based incidence data of childhood tuberculosis and adds valuable information to the global effort of producing better estimates, a critical step to inform public health policy.

Radiological findings in young children investigated for tuberculosis in Mozambique.

Introduction Chest radiography remains a critical tool for diagnosing intrathoracic tuberculosis (TB) in young children who are unable to expectorate. We describe the radiological findings in children under 3 years of age investigated for TB in the district of Manhiça, southern Mozambique, an area with a high prevalence of TB and HIV. Methods Digital antero-posterior and lateral projections were performed and reviewed by two independent readers, using a standardized template. Readers included a local pediatrician and a pediatric radiologist blinded to all clinical information. International consensus case definitions for intra-thoracic TB in children were applied. Results A total of 766 children were evaluated of whom 43 (5.6%) had TB. The most frequent lesion found in TB cases was air space consolidation (65.1%), followed by suggestive hilar lymphadenopathy (17.1%) and pleural effusion (7.0%). Air space consolidation was significantly more common in TB cases than in non-TB cases (odds ratio 8.9; 95% CI: 1.6-50.5), as were hilar lymphadenopathy (OR 17.2; 95% CI: 5.7-52.1). The only case with miliary infiltrates and 3 with pleural effusions occurred in HIV-infected children. Conclusion Frequent air space consolidation complicates radiological distinction between TB and bacterial pneumonia in young children, underscoring the need for epidemiological contextualization and consideration of all relevant signs and symptoms.

Trends in Cancer Incidence in Maputo, Mozambique, 1991–2008

Background Very limited information is available regarding the incidence of cancer in sub-Saharan Africa. We analyzed changes in cancer patterns from 1991 to 2008 in Maputo (Mozambique). Methods We calculated the rates of incidence of different cancer sites by sex in the 5-year age-group of the population of Maputo city as well as age-standardized rates (ASRs) and average annual percentage changes (AAPC). Results Over the 18-year study period a total of 12,674 cases of cancer (56.9% females) were registered with an overall increase in the risk of cancer in both sexes. In males, the most common cancers were those of the prostate, Kaposi sarcoma (KS) and the liver. Prostate cancer showed the most dramatic increase over the whole study period (AAPC +11.3%; 95% CI: 9.7–13.0), with an ASR of 61.7 per 105 in 2003–2008. In females, the most frequent cancers were of the uterine cervix, the breast and KS, with the former increasing along the whole study period (AAPC + 4.7%; 95% CI: 3.4–6) with an ASR of 62.0 per 105 in 2003–2008 as well as breast cancer (AAPC +6.5%; 95%CI: 4.3–8.7). Conclusions Overall, the risk of cancer rose in both sexes during the study period, particularly among cancers associated with westernization of lifestyles (prostate, breast), combined with increasingly rising incidences or limited changes in cancers associated with infection and poverty (uterine cervix, liver). Moreover, the burden of AIDS-associated cancers has shown a marked increase.

Intradermal HIV-1 DNA immunization using needle-free Zetajet TM injection followed by HIV-modified vaccinia virus Ankara vaccination is safe and immunogenic in Mozambican young adults: a phase I randomized controlled trial.

We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.2 ml) of HIV-DNA (3 mg/ml), followed by two boosts of 108 pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Envelope (Env). After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher dose group (median 420 vs. 157.5 SFC/million peripheral blood mononuclear cell, p = .014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 ml using Zetajet was safe and well tolerated. Priming with the 1,200 μg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

Seroepidemiology of Rubella in Mozambique, 2006-2014: Implications for Rubella Immunization in Settings With High Fertility Rates.

Background: Rubella and congenital rubella syndrome are highly underreported and neglected in most sub-Saharan countries and vaccination has not yet been incorporated into their national immunization schedules. In this study, we investigated the frequency of immunoglobulin M antibodies against rubella and examined correlations with fertility rates during the period from 2006 to 2014 in Mozambique. Methods: We conducted a retrospective analysis of data collected through the routine case-based surveillance system for measles in Mozambique. Results: A total of 7312 serum samples from suspected cases of measles were tested between 2006 and 2014. The median age was 4 years (interquartile range: 1–8 years). Of these, 1331 (18.2%) were positive for immunoglobulin M anti-rubella. The highest frequency of rubella was observed within the 5–9-year-old age group (32.6%). The frequency in the age groups <1 years old, 1–4, 10–14, 15–19, 20–29 and ≥30 were 4.5%, 13.1%, 28.7%,18.7%, 5.2% and 5.1%, respectively. Conclusion: Our data show that rubella is frequent among women of childbearing age in Mozambique. Considering that early pregnancy is common in Mozambique, this suggests that, in settings such as ours, the introduction of routine rubella vaccination in children should be accompanied by repeated vaccination campaigns targeting older children and adolescents.

A pragmatic randomised controlled trial on routine iron prophylaxis during pregnancy in Maputo, Mozambique (PROFEG): rationale, design, and success

The effects of prophylactic iron during pregnancy on maternal and child health in developing settings with endemic malaria and high prevalence of HIV remain unclear. This paper describes the rationale, implementation and success of a pragmatic randomised controlled trial comparing routine iron supplementation vs. screening and treatment for anaemia during pregnancy. The setting was two health centres in Maputo, Mozambique. Pregnant women (≥ 12-week gestation; ≥ 18 years old; and not with a high-risk pregnancy, n=4326) were recruited. The main outcomes are preterm delivery and low birthweight. The women were randomly assigned to one of two iron administration policies: a routine iron group (n=2184) received 60 mg of ferrous sulphate plus 400 μg of folic acid daily while a selective iron group (n=2142) had screening and treatment for anaemia and a daily intake of 1 mg of folic acid. The recruitment, follow-up, and collection of follow-up data were successful; both groups were similar to each other in all the trial stages. Collection of delivery data was challenging and data on about 40% of births is missing. These are currently being traced through different hospitals and health centres. The compliance of the study personnel and the women with regard to regular measurement of haemoglobin and intake of the iron and folic acid tablets was high and similar in both trial arms. Taking into account the various constraints encountered, the stages of the present trial prior to delivery were carried out well.

Health and socio-demographic profile of women of reproductive age in rural communities of southern Mozambique

Reliable statistics on maternal morbidity and mortality are scarce in low and middle-income countries, especially in rural areas. This is the case in Mozambique where many births happen at home. Furthermore, a sizeable number of facility births have inadequate registration. Such information is crucial for developing effective national and global health policies for maternal and child health. The aim of this study was to generate reliable baseline socio-demographic information on women of reproductive age as well as to establish a demographic surveillance platform to support the planning and implementation of the Community Level Intervention for Pre-eclampsia (CLIP) study, a cluster randomized controlled trial. This study represents a census of all women of reproductive age (12–49 years) in twelve rural communities in Maputo and Gaza provinces of Mozambique. The data were collected through electronic forms implemented in Open Data Kit (ODK) (an app for android based tablets) and household and individual characteristics. Verbal autopsies were conducted on all reported maternal deaths to determine the underlying cause of death. Between March and October 2014, 50,493 households and 80,483 women of reproductive age (mean age 26.9 years) were surveyed. A total of 14,617 pregnancies were reported in the twelve months prior to the census, resulting in 9,029 completed pregnancies. Of completed pregnancies, 8,796 resulted in live births, 466 resulted in stillbirths and 288 resulted in miscarriages. The remaining pregnancies had not yet been completed during the time of the survey (5,588 pregnancies). The age specific fertility indicates that highest rate (188 live births per 1,000 women) occurs in the age 20–24 years old. The estimated stillbirth rate was 50.3/1,000 live and stillbirths; neonatal mortality rate was 13.3/1,000 live births and maternal mortality ratio was 204.6/100,000 live births. The most common direct cause of maternal death was eclampsia and tuberculosis was the most common indirect cause of death. This study found that fertility rate is high at age 20–24 years old. Pregnancy in the advanced age (>35 years of age) in this study was associated with higher poor outcomes such as miscarriage and stillbirth. The study also found high stillbirth rate indicating a need for increased attention to maternal health in southern Mozambique. Tuberculosis and HIV/AIDS are prominent indirect causes of maternal death, while eclampsia represents the number one direct obstetric cause of maternal deaths in these communities. Additional efforts to promote safe motherhood and improve child survival are crucial in these communities.

Progress in Mozambique: Changes in the availability, use, and quality of emergency obstetric and newborn care between 2007 and 2012

Introduction Maternal mortality in Mozambique has not declined significantly in the last 10–15 years, plateauing around 480 maternal deaths per 100,000 live births. Good quality antenatal care and routine and emergency intrapartum care are critical to reducing preventable maternal and newborn deaths. Materials and methods We compare the findings from two national cross-sectional facility-based assessments conducted in 2007 and 2012. Both were designed to measure the availability, use and quality of emergency obstetric and neonatal care. Indicators for monitoring emergency obstetric care were used as were descriptive statistics. Results The availability of facilities providing the full range of obstetric life-saving procedures (signal functions) decreased. However, an expansion in the provision of individual signal functions was highly visible in health centers and health posts, but in hospitals, performance was less satisfactory, with proportionally fewer hospitals providing assisted vaginal delivery, obstetric surgery and blood transfusions. All other key indicators showed signs of improvements: the institutional delivery rate, the cesarean delivery rate, met need for emergency obstetric care (EmOC), institutional stillbirth and early neonatal death rates, and cause-specific case fatality rates (CFRs). CFRs for most major obstetric complications declined between 17% and 69%. The contribution of direct causes to maternal deaths decreased while the proportion of indirect causes doubled during the five-year interval. Conclusions The indicator of EmOC service availability, often used for planning and developing EmONC networks, requires close examination. The standard definition can mask programmatic weaknesses and thus, fails to inform decision makers of what to target. In this case, the decline in the use of assisted vaginal delivery explained much of the difference in this indicator between the two surveys, as did faltering hospital performance. Despite this backsliding, many signs of improvement were also observed in this 5-year period, but indicator levels continue below recommended thresholds. The quality of intrapartum care and the adverse consequences from infectious diseases during pregnancy point to priority areas for programmatic improvement.

Clinical and epidemiological characterization of influenza virus infections in children with severe acute respiratory infection in Maputo, Mozambique: Results from the implementation of sentinel surveillance, 2014 – 2016

In Sub-Saharan Africa, where burden, impact, and incidence of acute respiratory infections (ARI) are the highest in the world, conversely, the epidemiology of influenza-associated severe acute respiratory infections (SARI) is incompletely known. The aim of this study was to describe the clinical and epidemiological features of influenza-associated SARI in hospitalized children in Maputo city, Mozambique. Nasopharyngeal and oropharyngeal swabs were collected from children aged 0–14 years old who met the case definition for SARI in two hospitals in Maputo city after their parents or legal representative consented to participate. A structured questionnaire was used to collect clinical and demographic data. Typing and subtyping of influenza were performed by real-time PCR. From January 2014 to December 2016, a total of 2,007 eligible children were recruited, of whom 1,997 (99.5%) were screened for influenza by real-time PCR. The median age of participants was 16.9 months (IQR: 7.0–38.9 months) and 53.9% (1076/1991) were male. A total of 77 were positive for influenza, yielding a frequency of 3.9% (77/1,991), with the highest frequency being reported in the age group 1–5 years old. Cases of influenza peaked twice each year, during which, its frequency reached up to 60%-80%. Among all influenza confirmed cases, 33.7% (26/77), 35.1% (27/77) and 28.6% (22/77) were typed as influenza A/H3N2, A/H1N1pdm09, and B, respectively. This represents the first report of influenza in urban/sub urban setting in Mozambique and the first evidence of distribution of strains of influenza in the country. Our data showed that frequency of influenza was lower than reported in a rural setting in Mozambique and the frequency of seasonal (A/H1N1pdm09) and (A/H3N2) subtypes were similar in children with SARI.

External Quality Assessment Programme for Early Infant Diagnosis of HIV-1, Mozambique, 2011–2014

This study evaluated a National External Quality Scheme Program for early infant diagnosis of HIV. Fourteen laboratory technicians participated and nine testing panel cycles were sent between 2011 and 2014. The response rate was 100% for the first eight panels, and the number of technicians with a test score of 100% increased during the first three panels. Based on the evaluations of the technicians, the quality of testing for early infant diagnosis of HIV improved over time in the laboratories.