Over-diagnosis of malaria is not a lost cause.

BACKGROUND: Recent studies have highlighted the over-diagnosis of malaria in clinical settings in Africa. This study assessed the impact of a training programme implemented as part of an intervention trial on diagnostic behaviour of clinicians in a rural district hospital in a low-moderate malaria transmission setting. METHODS: From the beginning of 2005, a randomized controlled trial (RCT) of intermittent preventive treatment for malaria in infants (IPTi) has been conducted at the study hospital. As part of the RCT, the study team offered laboratory quality assurance, and supervision and training of paediatric ward staff using information on malaria epidemiology in the community. Data on clinical and blood slide confirmed cases of malaria from 2001 to 2005 were extracted from the hospital records. RESULTS: The proportion of blood slides positive for malaria parasites had decreased from 21% in 2001 to 7% in 2005 (p < .01). The proportion of outpatient and inpatient cases diagnosed as malaria ranged between 34% and 28% from 2001 to 2004 and this decreased substantially to 17% after the introduction of the package of training and support in 2005 (p < .01). There was no clear trend in the ratio of blood slide examined versus total diagnosis of malaria. CONCLUSION: It may be possible to change the diagnostic behaviour of clinicians by rigorous training using local malaria epidemiology data and supportive supervision

A multicentre comparison of a novel surrogate marker for determining the specific potency of anti-tuberculosis drugs.

A model for evaluating the potency of a new anti-tuberculosis drug or a drug combination, based on a decline in the number of viable tubercle bacilli in patient's sputum during 5 days mono-therapy has been reported. One popular measure is based on the analysis of the decline in bacterial counts during the first 48 h of therapy and has been called early bactericidal activity (EBA). Such analyses could detect EBA for only a few drugs and were subject to variations in results obtained in different sites. To address these problems we applied a reiterative exponential decay model to evaluate the data on bacterial counts during 5 days of mono-therapy. The validity of this approach was tested using data from three previously published studies. For patients treated with isoniazid 300 mg daily, the values for the time taken to reduce the viable count by 50% (vt50) measured in days were, from a Kenyan study 0.58 days S.E.M. 0.18, from a Tanzanian study 0.41 days S.E.M. 0.04, and from a United States study 0.55 days s.e.m. 0.12. These differences were not statistically significant (P = 0.77 Kruskal-Wallis non-parametric ANOVA). Mean values of vt50 for all of the major anti-tuberculosis agents showed that there was an overlapping spectrum of activity from isoniazid 300 mg (vt50 0.58 days) to para-amino-salicylic acid (vt50 2.9 days) The variation between column means was greater than could be expected by chance (P = 0.0002 Kruskal-Wallis non-parametric ANOVA). From this, we conclude that the reiterative exponential decay model permits comparison between the data obtained in different centres and would allow the activity of a new drug to be compared with that of the currently available agents

An unusual case of meningococcal meningitis complicated with subdural empyema in a 3 month old infant: a case report

Subdural empyema is an unusual complication of meningococcal meningitis, and in acute cases can be rapidly fatal. We present a case of an 8 week old infant who presented with atypical Neisseria meningitis with bifrontal subdural empyema formation. Through the utilisation of modern polymerise chain reaction tests on cerebrospinal fluid samples, we were able to confirm the diagnosis and institute appropriate treatment. Early surgical intervention and appropriate intravenous antibiotics meant that the patient fully recovered. In summary, early treatment of meningitis without adequate microbiological investigations can complicate later diagnosis of subdural empyema. Early suspicion of empyema should be considered when patient fails to improve after 48 hrs, seizures are a late sign and gives a poorer prognosis. Computed tomography scanning is still the modality of choice although in this case, magnetic resonance imaging had its benefits. Polymerase chain reaction of cerebrospinal fluid testing may also provide an important confirmatory test in future

A national policy for malaria elimination in Swaziland: a first for sub-Saharan Africa

Swaziland is working to be the first country in mainland sub-Saharan Africa to eliminate malaria. The highest level of Swaziland's government recently approved a national elimination policy, which endorses Swaziland's robust national elimination strategic plan. This commentary outlines Swaziland's progress towards elimination as well as the challenges that remain, primarily around securing long-term financial resources and managing imported cases from neighbouring countries

Mapping malaria risk in low transmission settings: challenges and opportunities

As malaria transmission declines, it becomes increasingly focal and prone to outbreaks. Understanding and predicting patterns of transmission risk becomes an important component of an effective elimination campaign, allowing limited resources for control and elimination to be targeted cost-effectively. Malaria risk mapping in low transmission settings is associated with some unique challenges. This article reviews the main challenges and opportunities related to risk mapping in low transmission areas including recent advancements in risk mapping low transmission malaria, relevant metrics, and statistical approaches and risk mapping in post-elimination settings

Insecticide resistance and the future of malaria control in Zambia.

BACKGROUND: In line with the Global trend to improve malaria control efforts a major campaign of insecticide treated net distribution was initiated in 1999 and indoor residual spraying with DDT or pyrethroids was reintroduced in 2000 in Zambia. In 2006, these efforts were strengthened by the President's Malaria Initiative. This manuscript reports on the monitoring and evaluation of these activities and the potential impact of emerging insecticide resistance on disease transmission. METHODS: Mosquitoes were captured daily through a series of 108 window exit traps located at 18 sentinel sites. Specimens were identified to species and analyzed for sporozoites. Adult Anopheles mosquitoes were collected resting indoors and larva collected in breeding sites were reared to F1 and F0 generations in the lab and tested for insecticide resistance following the standard WHO susceptibility assay protocol. Annual cross sectional household parasite surveys were carried out to monitor the impact of the control programme on prevalence of Plasmodium falciparum in children aged 1 to 14 years. RESULTS: A total of 619 Anopheles gambiae s.l. and 228 Anopheles funestus s.l. were captured from window exit traps throughout the period, of which 203 were An. gambiae malaria vectors and 14 An. funestus s.s.. In 2010 resistance to DDT and the pyrethroids deltamethrin, lambda-cyhalothrin and permethrin was detected in both An. gambiae s.s. and An. funestus s.s.. No sporozoites were detected in either species. Prevalence of P. falciparum in the sentinel sites remained below 10% throughout the study period. CONCLUSION: Both An. gambiae s.s. and An. funestus s.s. were controlled effectively with the ITN and IRS programme in Zambia, maintaining a reduced disease transmission and burden. However, the discovery of DDT and pyrethroid resistance in the country threatens the sustainability of the vector control programme

Epidemiology of Subpatent Plasmodium Falciparum Infection: Implications for Detection of Hotspots with Imperfect Diagnostics.

At the local level, malaria transmission clusters in hotspots, which may be a group of households that experience higher than average exposure to infectious mosquitoes. Active case detection often relying on rapid diagnostic tests for mass screen and treat campaigns has been proposed as a method to detect and treat individuals in hotspots. Data from a cross-sectional survey conducted in north-western Tanzania were used to examine the spatial distribution of Plasmodium falciparum and the relationship between household exposure and parasite density. Dried blood spots were collected from consenting individuals from four villages during a survey conducted in 2010. These were analysed by PCR for the presence of P. falciparum, with the parasite density of positive samples being estimated by quantitative PCR. Household exposure was estimated using the distance-weighted PCR prevalence of infection. Parasite density simulations were used to estimate the proportion of infections that would be treated using a screen and treat approach with rapid diagnostic tests (RDT) compared to targeted mass drug administration (tMDA) and Mass Drug Administration (MDA). Polymerase chain reaction PCR analysis revealed that of the 3,057 blood samples analysed, 1,078 were positive. Mean distance-weighted PCR prevalence per household was 34.5%. Parasite density was negatively associated with transmission intensity with the odds of an infection being subpatent increasing with household exposure (OR 1.09 per 1% increase in exposure). Parasite density was also related to age, being highest in children five to ten years old and lowest in those > 40 years. Simulations of different tMDA strategies showed that treating all individuals in households where RDT prevalence was above 20% increased the number of infections that would have been treated from 43 to 55%. However, even with this strategy, 45% of infections remained untreated. The negative relationship between household exposure and parasite density suggests that DNA-based detection of parasites is needed to provide adequate sensitivity in hotspots. Targeting MDA only to households with RDT-positive individuals may allow a larger fraction of infections to be treated. These results suggest that community-wide MDA, instead of screen and treat strategies, may be needed to successfully treat the asymptomatic, subpatent parasite reservoir and reduce transmission in similar settings

A qualitative study to assess community barriers to malaria mass drug administration trials in The Gambia.

BACKGROUND: Mass drug administration (MDA) is a strategy widely used in the control of human parasitic diseases but has been rarely attempted with malaria, the most common and dangerous parasitic disease in humans. MDA is an intervention strategy that involves simultaneously dispensing treatment to an entire population in a given geographic area. With some areas in sub-Saharan Africa documenting a decline in malaria transmission, the feasibility of MDA to further reduce malaria transmission is being considered. Understanding community perceptions of such an activity is vitally important for the design of the study and gaining the support of participants in order to maximize compliance and adherence. METHODS: A qualitative study to assess factors likely to influence community acceptance of MDA in the seasonal and low malaria transmission setting of The Gambia was conducted. Using in-depth interviews, the perceptions, knowledge and attitudes of medical personnel and community members who have undergone MDA trials in The Gambia were investigated. RESULTS: Several major themes emerged, namely: 1) the importance of timing of rounds of MDA doses for maximum participation; 2) the need to educate the target population with accurate information on the procedures, drug regimen, and possible side effects to enhance adherence; 3) the need for continuous sensitization meetings to maintain and increase uptake of MDA; and, 4) the importance for defining roles in the delivery and assessment of MDA, including existing healthcare structures. DISCUSSION: To increase the likelihood of participation in MDA trials in this setting, activities should be undertaken just before and during the rainy season when community members are less mobile. Importantly, fears regarding blood sampling and side effects of the drug regimen need to be addressed prior to the start of the trial and repeated throughout the study period. Accurate and frequent communication is essential, and village leaders should consistently be included in sensitization meetings to enhance community participation. Additionally, village healthcare workers should be included in training and implementation, with supervision by a fieldworker permanently posted in every few villages during the trial. Future collaboration with Senegal may prove important for enhanced elimination efforts in The Gambia

The effect of monthly sulfadoxine-pyrimethamine, alone or with azithromycin, on pcr-diagnosed malaria at delivery: A randomized controlled trial

10.1371/journal.pone.0041123PLoS ONE77