The role of antimalarial treatment in the elimination of malaria.

With declining transmission of malaria in several regions of the world and renewed interest in the elimination of malaria, strategies for malaria control using antimalarial drugs are being revisited. Drug-based strategies to reduce transmission of malaria need to target the asymptomatic carriers of infection. Drugs that are effective against gametocytes are few in number, but it may be possible to reduce gametocyte production by killing the asexual stages, for which more drugs are available. Drugs for use in large-scale programmes must be safe and tolerable. Strategies include improving access to treatment for malaria with an efficacious drug, intermittent-treatment programmes, and mass drug administration, with and without screening for malaria. Recent proposals have targeted high-risk groups for interventions. None of the strategies has been rigorously tested with appropriate control groups for comparison. Because of the lack of field evidence, modelling has been used. Models have shown, first, that for long-lasting effects, drug administration programmes should be linked with vector control, and second, that if elimination is the aim, programmes are likely to be more successful when applied to smaller populations of a few thousand or less. In order to sustain the gains following the scaling up of vector control and use of artemisinin combination therapies (ACTs), strategies that use antimalarials effectively need to be devised and evidence generated for the most cost-efficient way forward.

Intermittent preventive treatment of malaria in infants: how does it work and where will it work?

We discuss the potential public health impact of IPTi by estimating the cases of malaria, anaemia and hospital admissions likely to be averted in different transmission settings; and we review the mechanism of action, choice of drugs regimens, and the effect on immunity of IPTi. IPTi using an efficacious drug is likely to substantially reduce cases of clinical malaria in moderate to high transmission settings. However, geographical heterogeneity in malaria transmission could hamper rolling out IPTi as a national policy.

Prevalences of Pneumocystis jiroveci, Mycobacterium tuberculosis and Streptococcus pneumoniae infection in children with severe pneumonia, in a tertiary referral hospital in northern Tanzania.

At the Kilimanjaro Christian Medical Centre, a tertiary referral hospital in northern Tanzania, both the number of paediatric cases of lower respiratory-tract infection (LRTI) and the associated mortality increased between 2000 and 2001. Molecular diagnostic tools were used to enhance the identification of the pathogens responsible for this perceived increase. All 72 children aged between 2 and 60 months who were admitted with LRTI over a 3-month period were enrolled in the study. Induced sputum was collected from each child and, if the parents consented, the subjects were also tested for HIV. The sputum samples were each checked for bacteria by culture and, in amplification assays, for the DNA of Pneumocystis jiroveci, Mycobacterium tuberculosis and Streptococcus pneumoniae. Twenty-two (50%) of the 44 children tested for HIV had HIV-1 antibodies. Although only two children, both aged <6 months, were found PCR-positive for P. jiroveci, and only one was found positive for M. tuberculosis, 46 (including one of those found positive for P. jiroveci and the child found positive for M. tuberculosis) were found PCR-positive for S. pneumoniae. It therefore appears that most paediatric cases of LRTI who present at the hospital are attributable to S. pneumoniae, and that infections with this pathogen are entirely responsible for the observed increase in the incidence of LTRI in the local children. The increase seen in LRTI-associated mortality among the children may be the result of pneumococcal antibiotic resistance.

Mycobacterium tuberculosis lineage: a naming of the parts.

There have been many reports of groups of related Mycobacterium tuberculosis strains described variously as lineages, families or clades. There is no objective definition of these groupings, making it impossible to define relationships between those groups with biological advantages. Here we describe two groups of related strains obtained from an epidemiological study in Tanzania, which we define as the Kilimanjaro and Meru lineages on the basis of IS6110 restriction fragment length polymorphism (RFLP), polymorphic GC rich sequence (PGRS) RFLP and mycobacterial interspersed repeat unit (MIRU) typing. We investigated the concordance between each of the typing techniques and the dispersal of the typing profiles from a core pattern. The Meru lineage is more dispersed than the Kilimanjaro lineage and we speculate that the Meru lineage is older. We suggest that this approach provides an objective definition that proves robust in this epidemiological study. Such a framework will permit associations between a lineage and clinical or bacterial phenomenon to be tested objectively. This definition will also enable new putative lineages to be objectively tested.

Prospective evaluation of BDProbeTec strand displacement amplification (SDA) system for diagnosis of tuberculosis in non-respiratory and respiratory samples.

Nucleic acid amplification techniques (NAATs) have been demonstrated to make significant improvements in the diagnosis of tuberculosis (TB), particularly in the time to diagnosis and the diagnosis of smear-negative TB. The BD ProbeTec strand displacement amplification (SDA) system for the diagnosis of pulmonary and non-pulmonary tuberculosis was evaluated. A total of 689 samples were analysed from patients with clinically suspected TB. Compared with culture, the sensitivity and specificity for pulmonary samples were 98 and 89 %, and against final clinical diagnosis 93 and 92 %, respectively. This assay has undergone limited evaluation for non-respiratory samples and so 331 non-respiratory samples were tested, identifying those specimens that were likely to yield a useful result. These were CSF (n = 104), fine needle aspirates (n = 64) and pus (n = 41). Pleural fluid (n = 47) was identified as a poor specimen. A concern in using the SDA assay was that low-positive samples were difficult to interpret; 7.8 % of specimens fell into this category. Indeed, 64 % of the discrepant results, when compared to final clinical diagnosis, could be assigned as low-positive samples. Specimen type did not predict likelihood of a sample being in the low-positive zone. Although the manufacturers do not describe the concept of a low-positive zone, we have found that it aids clinical diagnosis.

Fusarium dimerum infection in a stem cell transplant recipient treated successfully with voriconazole.

We report the first case, to our knowledge, of a proven Fusarium dimerum soft-tissue infection in a stem cell transplant recipient treated successfully with voriconazole. There is a well-documented increase in the incidence, diversity and antifungal resistance of invasive mould infections in the immunocompromised patient population. The management of these infections is changing as new, more efficacious and less toxic antifungal agents become available. We present the case of a 19-year-old female diagnosed with a proven F. dimerum soft-tissue infection of the foot and possible pulmonary infection with the same organism 10 days following a sibling allogeneic stem cell transplant for severe aplastic anaemia. The infection developed despite treatment with 3 mg/kg AmBisome for a concurrent chest infection. She was treated successfully with voriconazole.