Tuberculosis drug resistance in Southern Mozambique: results of a population-level survey in the district of Manhiça.

SETTING: Mozambique, one of the world's high tuberculosis (TB) burden countries, has conducted only one national-level drug resistance survey, in 2007-2008. OBJECTIVE: To determine the drug resistance patterns of laboratory-confirmed TB cases. DESIGN: This was a population-level survey conducted over a 1-year period in the district of Manhiça. All laboratory-confirmed cases were evaluated for first-line anti-tuberculosis drug susceptibility testing using liquid culture. RESULTS: Resistance to at least one first-line drug was observed in 44 of 276 isolates (15.9%). Prevalence of drug resistance to each of the five anti-tuberculosis drugs tested was 4.0% for streptomycin, 10.1% for isoniazid (INH), 6.2% for rifampicin, 3.6% for ethambutol and 1.1% for pyrazinamide. The overall prevalence of multidrug-resistant TB (MDR-TB) was 5.1%: 3.8% (95%CI 2.0-7.0) in new and 13.2% (95%CI 5.8-27.3) in retreatment cases. Respectively 4.6% and 2.6% of new and retreatment cases were INH-monoresistant. Previous history of anti-tuberculosis treatment was associated with having MDR-TB (OR 4.3, 95%CI 1.3-14.1). CONCLUSION: The prevalence of drug resistance in the district of Manhiça is slightly higher than, but still compatible with, previous national estimates. INH monoresistance was high, posing the risk of hidden monotherapy in the continuation phase.

Sleeping arrangements and mass distribution of bed nets in six districts in central and northern Mozambique

Objective: Universal coverage with insecticide-treated bed nets is a cornerstone of modern malaria control. Mozambique has developed a novel bed net allocation strategy, where the number of bed nets allocated per household is calculated on the basis of household composition and assumptions about who sleeps with whom. We set out to evaluate the performance of the novel allocation strategy. Methods: A total of 1994 households were visited during household surveys following two universal coverage bed net distribution campaigns in Sofala and Nampula provinces in 2010-2013. Each sleeping space was observed for the presence of a bed net, and the sleeping patterns for each household were recorded. The observed coverage and efficiency were compared to a simulated coverage and efficiency had conventional allocation strategies been used. A composite indicator, the product of coverage and efficiency, was calculated. Observed sleeping patterns were compared with the sleeping pattern assumptions. Results: In households reached by the campaign, 93% (95% CI: 93-94%) of sleeping spaces in Sofala and 84% (82-86%) in Nampula were covered by campaign bed nets. The achieved efficiency was high, with 92% (91-93%) of distributed bed nets in Sofala and 93% (91-95%) in Nampula covering a sleeping space. Using the composite indicator, the novel allocation strategy outperformed all conventional strategies in Sofala and was tied for best in Nampula. The sleeping pattern assumptions were completely satisfied in 66% of households in Sofala and 56% of households in Nampula. The most common violation of the sleeping pattern assumptions was that male children 3-10 years of age tended not to share sleeping spaces with female children 3-10 or 10-16 years of age. Conclusions: The sleeping pattern assumptions underlying the novel bed net allocation strategy are generally valid, and net allocation using these assumptions can achieve high coverage and compare favourably with conventional allocation strategies.

Sleeping arrangements and mass distribution of bed nets in six districts in central and northern Mozambique.

OBJECTIVE: Universal coverage with insecticide-treated bed nets is a cornerstone of modern malaria control. Mozambique has developed a novel bed net allocation strategy, where the number of bed nets allocated per household is calculated on the basis of household composition and assumptions about who sleeps with whom. We set out to evaluate the performance of the novel allocation strategy. METHODS: A total of 1994 households were visited during household surveys following two universal coverage bed net distribution campaigns in Sofala and Nampula provinces in 2010-2013. Each sleeping space was observed for the presence of a bed net, and the sleeping patterns for each household were recorded. The observed coverage and efficiency were compared to a simulated coverage and efficiency had conventional allocation strategies been used. A composite indicator, the product of coverage and efficiency, was calculated. Observed sleeping patterns were compared with the sleeping pattern assumptions. RESULTS: In households reached by the campaign, 93% (95% CI: 93-94%) of sleeping spaces in Sofala and 84% (82-86%) in Nampula were covered by campaign bed nets. The achieved efficiency was high, with 92% (91-93%) of distributed bed nets in Sofala and 93% (91-95%) in Nampula covering a sleeping space. Using the composite indicator, the novel allocation strategy outperformed all conventional strategies in Sofala and was tied for best in Nampula. The sleeping pattern assumptions were completely satisfied in 66% of households in Sofala and 56% of households in Nampula. The most common violation of the sleeping pattern assumptions was that male children 3-10 years of age tended not to share sleeping spaces with female children 3-10 or 10-16 years of age. CONCLUSIONS: The sleeping pattern assumptions underlying the novel bed net allocation strategy are generally valid, and net allocation using these assumptions can achieve high coverage and compare favourably with conventional allocation strategies.

High HIV prevalence in a southern semi-rural area of Mozambique: a community-based survey.

BACKGROUND: Southern African countries have borne the brunt of the HIV/AIDS pandemic. Monitoring epidemiological dynamics is critical to identify the populations at greatest risk of infection and to guide control strategies. METHODS: A cross-sectional community-based study to determine age- and sex-specific HIV prevalence among individuals aged 18-47 years was carried out in Manhiça, southern Mozambique. Participants were randomly selected from the demographic surveillance system in place in the area and voluntary HIV counselling and testing were offered at home. In addition, HIV prevalence estimates from the antenatal clinic (ANC) were collected prospectively. RESULTS: A total of 839 individuals were invited to participate in the study. Of these, 722 were recruited (50.7% women). The overall HIV prevalence in the community was 39.9% [95% confidence interval (CI) 35.9-43.8%]. By age, the prevalence was 23.2% (95% CI 17.9-28.6%) in individuals aged 18-27 years, 41.2% (95% CI 35.6-48.3%) in those aged 28-37 years and 44.8% (95% CI 38.4-51.2%) in those aged 38-47 years. HIV prevalence was higher among women than men in all age groups. The overall HIV prevalence estimate for women in the community (43.1%; 95% CI 37.6-48.5%) was 1.4 times higher than that for those attending the ANC (29.4%; 95% CI 26.7-32.0%). CONCLUSIONS: The high HIV prevalence found in this region suggests that the epidemic is in a mature stable phase. The lower rates in the ANC than in the community suggest that ANC evaluations may underestimate community HIV prevalence. Resources to monitor HIV infection dynamics are needed to guide targeted control strategies in countries in which the epidemic exacts the greatest toll.

High HIV prevalence in a southern semi-rural area of Mozambique: a community-based survey

Background: Southern African countries have borne the brunt of the HIV/AIDS pandemic. Monitoring epidemiological dynamics is critical to identify the populations at greatest risk of infection and to guide control strategies. Methods: A cross-sectional community-based study to determine age- and sex-specific HIV prevalence among individuals aged 18-47 years was carried out in Manhiça, southern Mozambique. Participants were randomly selected from the demographic surveillance system in place in the area and voluntary HIV counselling and testing were offered at home. In addition, HIV prevalence estimates from the antenatal clinic (ANC) were collected prospectively. Results: A total of 839 individuals were invited to participate in the study. Of these, 722 were recruited (50.7% women). The overall HIV prevalence in the community was 39.9% [95% confidence interval (CI) 35.9-43.8%]. By age, the prevalence was 23.2% (95% CI 17.9-28.6%) in individuals aged 18-27 years, 41.2% (95% CI 35.6-48.3%) in those aged 28-37 years and 44.8% (95% CI 38.4-51.2%) in those aged 38-47 years. HIV prevalence was higher among women than men in all age groups. The overall HIV prevalence estimate for women in the community (43.1%; 95% CI 37.6-48.5%) was 1.4 times higher than that for those attending the ANC (29.4%; 95% CI 26.7-32.0%). Conclusions: The high HIV prevalence found in this region suggests that the epidemic is in a mature stable phase. The lower rates in the ANC than in the community suggest that ANC evaluations may underestimate community HIV prevalence. Resources to monitor HIV infection dynamics are needed to guide targeted control strategies in countries in which the epidemic exacts the greatest toll.

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.

Estimating the vaccine-preventable burden of hospitalized pneumonia among young Mozambican children.

Polysaccharide-protein conjugate vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae have proven efficacy against radiologically confirmed pneumonia. Measurement of pneumonia incidence provides a platform to estimate of the vaccine-preventable burden. Over 24 months, we conducted surveillance for radiologically confirmed severe pneumonia episodes among children <2 years of age admitted to a rural hospital in Manhiça, southern Mozambique. Study children were tested for HIV during the second year of surveillance. Severe pneumonia accounted for 15% of 5132 hospital admissions and 32% of in-hospital mortality among children <2 years of age. Also, 43% of chest radiographs were interpreted as radiologically confirmed pneumonia. HIV-infection was associated with 81% of fatal pneumonia episodes among children tested for HIV. The minimum incidence rate of radiologically confirmed pneumonia requiring hospitalization was 19 episodes/1000 child-years. Incidence rates among HIV-infected children were 9.3-19.0-fold higher than HIV-uninfected. Introduction of Hib and pneumococcal conjugate vaccines would have a substantial impact on pneumonia hospitalizations among African children if vaccine effects are similar to those observed in clinical trials.

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.