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.

A comparison of human metapneumovirus and respiratory syncytial virus WHO-defined severe pneumonia in Moroccan children.

Acute respiratory infections remain the principal cause of morbidity and mortality in Moroccan children. Besides bacterial infections, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are prominent among other viruses due to their high prevalence and association with severe clinical episodes. We aimed to describe and compare RSV- and hMPV-associated cases of WHO-defined severe pneumonia in a paediatric population admitted to Morocco's reference hospital. Children aged 2-59 months admitted to the Hôpital d'Enfants de Rabat, Morocco meeting WHO-defined severe pneumonia criteria were recruited during 14 months and thoroughly investigated to ascertain a definitive diagnosis. Viral prevalence of RSV, hMPV and other viruses causing respiratory symptoms was investigated in nasopharyngeal aspirate samples through the use of molecular methods. Of the 683 children recruited and included in the final analysis, 61/683 (8·9%) and 124/683 (18·2%) were infected with hMPV and RSV, respectively. Besides a borderline significant tendency for higher age in hMPV cases, patients infected with either of the viruses behaved similarly in terms of demographics, patient history, past morbidity and comorbidity, vaccination history, socioeconomic background and family environment. Clinical presentation on arrival was also similar for both viruses, but hMPV cases were associated with more severity than RSV cases, had a higher risk of intensive care need, and received antibiotic treatment more frequently. RSV and hMPV are common and potentially life-threatening causes of WHO-defined pneumonia in Moroccan children. Both viruses show indistinctive clinical symptomatology, but in Moroccan children, hMPV was associated with a more severe evolution.

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 prevalence of Pneumocystis jirovecii pneumonia among Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia.

We aimed to describe Pneumocystis jirovecii pneumonia (PCP) prevalence and features in children from sub-Saharan Africa and to investigate PCP-associated risk factors. During 2006-2007 we used molecular methods to test children younger than 5 years old admitted with severe pneumonia to a hospital in southern Mozambique for Pneumocystis infection. We recruited 834 children. PCP prevalence was 6.8% and HIV prevalence was 25.7%. The in-hospital and delayed mortality were significantly higher among children with PCP (20.8% vs. 10.2%, p 0.021, and 11.5% vs. 3.6%, p 0.044, respectively). Clinical features were mostly overlapping between the two groups. Independent risk factors for PCP were age less than a year (odds ratio (OR) 6.34, 95% confidence interval (CI) 1.86-21.65), HIV infection (OR 2.99, 95% CI 1.16-7.70), grunting (OR 2.64, 95% CI 1.04-6.73) and digital clubbing (OR 10.75, 95% CI 1.21-95.56). PCP is a common and life-threatening cause of severe pneumonia in Mozambican children. Mother-to-child HIV transmission prevention should be strengthened. Better diagnostic tools are needed.

Massive Plasmodium falciparum visceral sequestration: a cause of maternal death in Africa.

Sequestration of Plasmodium falciparum-infected erythrocytes (PfIE) in the capillaries of the central nervous system (CNS) is the pathognomonic feature of cerebral malaria, a condition frequently leading to death. Sequestration of PfIE in the placental intervillous spaces is the characteristic feature of malaria in pregnancy and is associated with low birthweight and prematurity. Although both patterns of sequestration are thought to result from the expression of different parasite proteins involved in cytoadhesion to human receptors, scant information exists on whether both conditions can coexist and whether this can lead to death. We conducted a prospective autopsy study including all consecutive pregnancy-related deaths in a tertiary-level referral hospital in Maputo, Mozambique, between October 2002 and December 2006. Extensive sampling of all major viscera was performed. All cases showing parasites in any of the viscera were included in the analysis. From 317 complete autopsies PfIEs were identified in ten women (3.2%). All cases showed massive accumulation of PfIE in small capillaries of the CNS but also in most visceral capillaries (heart, lung, kidney, uterus). Placental tissue, available in four cases, showed a massive accumulation of maternal PfIE in the intervillous space. Coma (six women) and dyspnoea (five women) were the most frequent presenting clinical symptoms. In conclusion, massive visceral sequestration of PfIE with significant involvement of the CNS is an infrequent but definite direct cause of maternal death in endemic areas of Africa. The PfIE sequestered in cerebral capillaries and the placenta coexist in these fatal cases.

Procalcitonin and C-reactive protein as predictors of blood culture positivity among hospitalised children with severe pneumonia in Mozambique.

OBJECTIVES: To evaluate the benefits of using procalcitonin (PCT) and C-reactive protein (CRP) as pre-screening tools to predict blood culture positivity among Mozambican children with clinical severe pneumonia (CSP). METHODS: 586 children <5 years with CSP and no concurrent malaria fulfilled criteria to be included in the study groups. We determined PCT and CRP for all children with positive bacterial culture (BC+ group, n = 84) and of a random selection of children with negative bacterial culture (BC- group, n = 246). RESULTS: PCT and CRP levels were higher in the BC+ group than the BC- one (PCT: median 7.73 versus 0.48 ng/ml, P < 0.001; CRP: 177.65 mg/l vs. 26.5 mg/l, P < 0.001). In multivariate analysis, PCT was the only independent predictor of the group. To be used as pre-screening tool, PCT presented higher specificities for predetermined sensitivities (≥85%) than CRP. Pursuing a sensitivity of 95%, PCT could reduce the need for bacterial culture by 49% and overall diagnosis costs by 7-35% [assuming variable costs for PCT measurement (ranging from 10 to 30 USD) and a fixed cost of 72.5 USD per blood culture]. CONCLUSIONS: Among hospitalised children with CSP and absence of concurrent malaria, PCT pre-screening could help reduce the number of blood cultures and diagnosis costs by specifically targeting patients more likely to yield positive results.

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.

Serotype-specific pneumococcal disease may be influenced by mannose-binding lectin deficiency.

Previous studies of the association between the mannose-binding lectin pathway deficiencies and invasive pneumococcal disease are inconclusive. Invasiveness of Streptococcus pneumoniae is dependent on serotype. We aimed to determine the association between invasive pneumococcal disease and MBL2 and MASP2 genetic variants, regarding serotype distribution. A hospital-based case-control study was conducted in children admitted to hospital in rural Mozambique in June 2002-November 2003. The study included children admitted to hospital with invasive pneumococcal disease, in whom S. pneumoniae was isolated from blood and subsequently serotyped. Sequence-based typing analysis of amplicons covering the polymorphic regions of MASP2 (exon 3) and MBL2 (promoter and exon 1) was performed. An overall high frequency of MBL2 genotypes associated with low serum levels of MBL (43%) was found. Carriers of MBL-deficient genotypes were associated with invasive pneumococcal disease produced by low-invasive serotypes (OR 5.55, 95% CI 1.4-21.9; p = 0.01). Our data suggest that susceptibility to pneumococcal disease among MBL-deficient patients may be influenced by serotype invasiveness. Type-specific capsular serotype of S. pneumoniae would need to be taken into account in further genetic association studies of invasive pneumococcal disease.