Clinical and operational factors associated with low pediatric inpatient HIV testing coverage in Mozambique.

SETTING: Eleven pediatric wards in Maputo Province, Mozambique. OBJECTIVE: 1) To determine provider-initiated testing and counseling (PITC) coverage, the rate of human immunodeficiency virus (HIV) positivity, and the clinical and facility-level variables associated with PITC; and 2) to assess the care cascade for HIV-exposed and -infected children. DESIGN: This was a cross-sectional, retrospective review of inpatient charts, selected via systematic randomization, of patients aged 0-4 years, admitted between July and December 2015. RESULTS: Among the 800 patients included, the median age was 23 months and median duration of hospitalization was 3 days. HIV testing was ordered in 46.0% of eligible patients (known HIV-infected at admission excluded), with results documented for 35.7%, of whom 8.3% were positive. The patient hospitalization diagnoses with the highest PITC rates were malnutrition (73.8%), sepsis (71.4%) and tuberculosis (58.3%), with positivity rates of respectively 16.1%, 20.0%, and 28.6%. Longer hospitalization, weekday admission, and PITC training for staff were significantly associated with better PITC performance. Antiretroviral treatment was initiated during hospitalization for 29.6% of eligible patients. CONCLUSION: PITC coverage was low, with high HIV positivity rates, highlighting missed opportunities for diagnosis and linkage to treatment. Strengthened routine testing on wards with consideration of inpatient ART initiation are needed to help achieve pediatric 90-90-90 goals.

A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants.

BACKGROUND: Several novel tuberculosis vaccines are currently in clinical trials, including AERAS-402, an adenovector encoding a fusion protein of Mycobacterium tuberculosis antigens 85A, 85B, and TB10.4. A multicentred trial of AERAS-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-Saharan Africa, using an adaptive design. METHODS: In a double-blind, randomised, placebo-controlled, dose-finding trial, we enrolled BCG-vaccinated, HIV-uninfected infants aged 16-26 weeks. Infants in the safety/dose-finding phase received two doses of AERAS-402 across three dose levels, or placebo, intramuscularly on days 0 and 28. Infants in the expanded safety phase received three doses of the highest dose level, with the 3rd dose at day 280. Follow up for safety and immunogenicity was for up to two years. RESULTS: We enrolled 206 infants (52 placebo and 154 AERAS-402 recipients) into the dose-finding phase and 281 (141 placebo and 140 AERAS-402 recipients) into the expanded safety phase. Safety data were acceptable across all dose levels. No vaccine-related deaths were recorded. A single serious adverse event of tachypnoea was deemed related to study vaccine. Antibodies directed largely against Ag85A and Ag85B were detected. Low magnitude CD4+ and CD8+ polyfunctional T cell responses were observed at all dose levels. The addition of a third dose of AERAS-402 at the highest dose level did not increase frequency or magnitude of antibody or CD8+ T cell responses. CONCLUSIONS: AERAS-402 has an acceptable safety profile in infants and was well tolerated at all dose levels. Response rate was lower than previously seen in BCG vaccinated adults, and frequency and magnitude of antigen-specific T cells were not increased by a third dose of vaccine.

Stabilization of HIV incidence in women of reproductive age in southern Mozambique.

INTRODUCTION: The collection of incidence data on HIV infection is necessary to evaluate the status and dynamics of the epidemic and the effectiveness of intervention strategies. However, this is usually difficult in low-income countries. METHODS: Five yearly point HIV prevalence estimations (in 1999, 2003, 2004, 2005 and 2008) were obtained for women between 15 and 45 years of age participating in three studies carried out for other purposes at the Antenatal Clinic (ANC) in Manhiça, Mozambique. HIV incidence was estimated between prevalence points using a previously validated methodology. Two methods were used, one based on mortality rates for three HIV epidemic scenarios, and the other based on survival information after infection. The pattern over time was captured by fitting a log-regression model. RESULTS: The prevalence of HIV infection ranged from 12% in 1999 to 49% in 2008. The HIV incidence increased from approximately 3.5 cases per 100 person-years in 2001 to 14 per 100 person-years in 2004, with stabilization thereafter to levels of around 12 cases per 100 person-years. The incidence estimates were comparable for the two methods used. CONCLUSION: These findings indicate an increase in the prevalence and incidence of HIV infection among women of reproductive age over the 9 years of the analysis, with a plateau in the incidence of infection since 2005. However, the very high figures for both prevalence and incidence highlight the importance of the continuation of the prevention and treatment programmes that already exist, and suggest that implementation of preventive measures is needed in this area.

Acute bacterial meningitis among children, in Manhiça, a rural area in Southern Mozambique

Introduction: Acute bacterial meningitis (ABM) is one of the most severe diseases in Sub-Saharan Africa. Although data for the continent is very limited, more than one million cases are estimated per year, with mortality and life-long sequelae occurring in 50% of these cases. Methods: As part of the clinical management of children admitted to the Manhiça District Hospital, information on cases of ABM was recorded. We analysed data from June 1998 to November 2003. Results: During the study period, 475 cerebrospinal-fluid (CSF) samples were collected from 20,173 children <15 years of age admitted to hospital. Culture results confirmed 71 (15%) cases of ABM. The most prevalent bacterial aetiologies were Streptotoccus pneumoniae (pneumococcus, n=31), Haemophilus influenzae (n=13) and Neisseria meningitis (n=8). Other important bacteria were Streptococcus sp. (n=7), Salmonella sp. (n=4) and Staphylococcus aureus (n=3). Crude incidence rates of ABM and pneumococcal meningitis were 20/100,000 and 10/100,000 children-year-at-risk, respectively. Incidences were more than three times higher in the <1 year age group. Overall case fatality rate was 36%, and was highest for H. influenzae and pneumococcal meningitis (55% and 45%, respectively, p=0.044). Pneumococcal susceptibility was 81% for oxacillin and 93% for chloramphenicol. For H. influenzae isolates, susceptibility was 54% for ampicillin and 62% for chloramphenicol. Conclusions: S. pneumoniae and H. influenzae are the main aetiologies responsible for the high burden of morbidity and mortality associated with ABM in rural Mozambique. These findings are important to evaluate treatment guidelines and potential impact of control measures

Acute bacterial meningitis among children, in Manhiça, a rural area in Southern Mozambique.

INTRODUCTION: Acute bacterial meningitis (ABM) is one of the most severe diseases in Sub-Saharan Africa. Although data for the continent is very limited, more than one million cases are estimated per year, with mortality and life-long sequelae occurring in 50% of these cases. METHODS: As part of the clinical management of children admitted to the Manhiça District Hospital, information on cases of ABM was recorded. We analysed data from June 1998 to November 2003. RESULTS: During the study period, 475 cerebrospinal-fluid (CSF) samples were collected from 20,173 children <15 years of age admitted to hospital. Culture results confirmed 71 (15%) cases of ABM. The most prevalent bacterial aetiologies were Streptotoccus pneumoniae (pneumococcus, n=31), Haemophilus influenzae (n=13) and Neisseria meningitis (n=8). Other important bacteria were Streptococcus sp. (n=7), Salmonella sp. (n=4) and Staphylococcus aureus (n=3). Crude incidence rates of ABM and pneumococcal meningitis were 20/100,000 and 10/100,000 children-year-at-risk, respectively. Incidences were more than three times higher in the <1 year age group. Overall case fatality rate was 36%, and was highest for H. influenzae and pneumococcal meningitis (55% and 45%, respectively, p=0.044). Pneumococcal susceptibility was 81% for oxacillin and 93% for chloramphenicol. For H. influenzae isolates, susceptibility was 54% for ampicillin and 62% for chloramphenicol. CONCLUSIONS: S. pneumoniae and H. influenzae are the main aetiologies responsible for the high burden of morbidity and mortality associated with ABM in rural Mozambique. These findings are important to evaluate treatment guidelines and potential impact of control measures.

Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in children aged 1-4 in Mozambique.

BACKGROUND: The development of a malaria vaccine remains a public health priority for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to be safe and immunogenic in previous studies in adults and staggered dose-escalation studies in children in The Gambia. However, genetic features and the intensity of malaria transmission may modify the safety and immune response of a vaccine. OBJECTIVE: We carried out a phase I, double-blind randomized controlled trial in 60 children aged 1-4 in Mozambique to evaluate the safety, reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb proof-of-concept of efficacy study in the same population. METHOD: Children were randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of safety and reactogenicity included detailed clinical and laboratory analyses and assessment of adverse events (AEs). RESULTS: The RTS,S/AS02A was found to be safe and well tolerated. Serious adverse events were balanced between both groups and none was related to vaccination. The frequency of adverse events reported with RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were infrequent (one case of pain, one of fever in each group and some swelling greater than 20 mm in diameter), transient and resolved without sequelae. RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody response and induced a strong anti-hepatitis-B surface antigen response.

Safety and immunogenicity of the RTS, S/AS02A candidate malaria vaccine in children aged 1­4 in Mozambique

The development of a malaria vaccine remains a public health priority for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to be safe and immunogenic in previous studies in adults and staggered dose-escalation studies in children in The Gambia. However, genetic features and the intensity of malaria transmission may modify the safety and immune response of a vaccine. We carried out a phase I, double-blind randomized controlled trial in 60 children aged 1-4 in Mozambique to evaluate the safety, reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb proof-of-concept of efficacy study in the same population. Children were randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of safety and reactogenicity included detailed clinical and laboratory analyses and assessment of adverse events (AEs). The RTS,S/AS02A was found to be safe and well tolerated. Serious adverse events were balanced between both groups and none was related to vaccination. The frequency of adverse events reported with RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were infrequent (one case of pain, one of fever in each group and some swelling greater than 20 mm in diameter), transient and resolved without sequelae. RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody response and induced a strong anti-hepatitis-B surface antigen response.

Invasive pneumococcal disease in children<5 years of age in rural Mozambique.

OBJECTIVES: To estimate the incidence and epidemiological characteristics of invasive pneumococcal disease (IPD) in children<5 years of age living in a rural area of southern Mozambique. METHODS: As part of the clinical management of children admitted to Manhiça District Hospital, prospective surveillance for invasive bacterial disease was conducted from June 2001 to May 2003. The level of antibiotic resistance of the isolates was also analysed. RESULTS: Pneumococcus was the most commonly isolated bacterium, accounting for 212 episodes. The estimated crude incidence rate of IPD in the study area among children<5 years of age was 416/100,000 per child-year at risk. The youngest age group (<3 months) had the highest incidence (779/100,000). Cases were detected during both rainy and dry seasons. The most common clinical diagnosis was pneumonia, made in 146/212 (69%) of the episodes of IPD. The overall case fatality rate was 10%, being highest among children with pneumococcal meningitis (5/9=56%). Pneumococcal isolates were highly susceptible to penicillin (86% susceptible and 14% with intermediate resistance) and chloramphenicol (98% susceptible). In contrast, up to 37% of the isolates tested were non-susceptible to cotrimoxazole. CONCLUSIONS: Incidence rates of IPD and associated mortality shown in this study highlight the need for pneumococcal vaccines in rural Africa, which must be effective in infants and young children.

Invasive pneumococcal disease in children<5 years of age in rural Mozambique

Objectivos Estimar a incidência e as características epidemiológicas do pneumococo invasivodoença (DPI) em crianças de <5 anos de idade residentes em uma área rural do sul de Moçambique.Métodos Como parte do manejo clínico de crianças internadas em Manhiçum Hospital Distrital,A vigilância prospectiva para doença bacteriana invasiva foi realizada de junho de 2001 a maio de 2003. OO nível de resistência antibiótica dos isolados também foi analisado.Resultados Pneumococcus foi a bactéria mais comumente isolada, correspondendo a 212 episódios. Oa taxa bruta de incidência estimada de DPI na área de estudo entre crianças <5 anos de idade foi de 416/100.000por criança-ano em risco. A faixa etária mais jovem (<3 meses) apresentou a maior incidência (779/100.000).Os casos foram detectados durante as estações chuvosa e seca. O diagnóstico clínico mais comum foipneumonia, feita em 146/212 (69%) dos episódios de DPI. A taxa de letalidade geral foi de 10%;sendo maior entre as crianças com meningite pneumocócica (5/9 » 56%). Os isolados de pneumococo foramaltamente suscetível à penicilina (86% suscetível e 14% com resistência intermediária) e clor-anfenicol (98% suscetível). Em contraste, até 37% dos isolados testados não foram suscetíveis acotrimoxazol.Conclusões As taxas de incidência de DPI e mortalidade associada apresentadas neste estudo evidenciam a necessidade devacinas pneumocócicas na África rural, que devem ser eficazes em lactentes e crianças pequenas.

Characteristics of drug resistance and HIV among tuberculosis patients in Mozambique.

SETTING: The rate of human immunodeficiency virus (HIV) seroprevalence among tuberculosis patients varies between 2% and 53% in Mozambique, depending on the region. Drug resistance surveillance has been performed in only a few cities in Mozambique. OBJECTIVES: To establish the extent of drug resistance in areas of Mozambique with different levels of HIV prevalence, to estimate the prevalence of HIV among tuberculosis (TB) patients, and to examine the association between drug resistance and HIV infection. DESIGN: All tuberculosis patients diagnosed at randomly selected health facilities over 9 months (September 1998 to June 1999) were enrolled in the study. Sputum was collected, smeared and cultured, and drug susceptibility tests were performed. Blood was tested for HIV in the respective provinces, and patients received pre-test and post-test counselling. RESULTS: Of 709 culture-positive cases, 25.5% were HIV-positive. HIV-positive patients were significantly more likely to have a prior history of treatment (OR 2.2; 95% CI 1.9-3.6) and resistance to both isoniazid and streptomycin (OR 2.3; 95% CI 1.3, 4.5). In patients with no history of prior tuberculosis treatment, the multidrug resistance rate was 3.4% and resistance to isoniazid and streptomycin (HS) was 5.2%. Any drug resistance was significantly more common among those with a history of prior treatment (OR 3.1; 95% CI 2.1-4.7), particularly resistance to HS (OR 4.5; 95% CI 2.6-7.9). CONCLUSIONS: This study demonstrates substantial levels of drug resistance in Mozambique. Differences in drug resistance between high and low HIV prevalence areas may be related to prior treatment.

The burden of disease in Maputo City, Mozambique: registered and autopsied deaths in 1994.

OBJECTIVE: To classify the causes of death in Maputo City, Mozambique, using the methods of the Global Burden of Disease study, in order to provide information for health policy-makers and to obtain a baseline for future studies in Maputo City and provincial capitals. METHODS: Data were taken from the Maputo City death register and autopsy records for 1994. FINDINGS: A total of 9011 deaths were recorded in the death register, representing a coverage of approximately 86%. Of these, 8114 deaths (92%) were classified by cause. Communicable, maternal, perinatal, and nutritional disorders accounted for 5319 deaths; noncommunicable diseases for 1834; and injuries for 961. The 10 leading causes of registered deaths were perinatal disorders (1643 deaths); malaria (928); diarrhoeal diseases (814); tuberculosis (456); lower respiratory infections (416); road-traffic accidents (371); anaemia (269); cerebrovascular diseases (269); homicide (188); and bacterial meningitis (178). CONCLUSIONS: Infectious diseases of all types, injuries, and cerebrovascular disease ranked as leading causes of death, according to both the autopsy records and the city death register. AIDS-related deaths were underreported. With HIV infection increasing rapidly, AIDS will add to the already high burden of infectious diseases and premature mortality in Maputo City. The results of the study indicate that cause of death is a useful outcome indicator for disease control programmes.