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BackgroundTuberculosis (TB) diagnosis continues to rely on sputum smear microscopy in many settings. We conducted a meta-analysis to estimate the percentage of children and adults with tuberculosis that are sputum smear positive.MethodsWe searched PubMed, MEDLINE, Embase, and Global Health databases for studies that included both children and adults with all forms of active TB. The pooled percentages of children and adults with smear positive TB were estimated using the inverse variance heterogeneity model. This review was registered in the PROSPERO database under registration number CRD42015015331.ResultsWe identified 20 studies meeting our inclusion criteria that reported smear positivity for a total of 18,316 children and 162,574 adults from 14 countries. The pooled percentage of paediatric TB cases that were sputum smear positive was 6.8 % (95 % Confidence Interval (CI) 2.2–12.2 %), compared with 52.0 % (95 % CI 40.0–64.0 %) among adult cases. Eight studies reported data separately for children aged 0–4 and 5–14. The percentage of children aged 0–4 that were smear positive was 0.5 % (95 % CI 0.0–1.9 %), compared with 14.0 % (95 % CI 8.9–19.4 %) among children aged 5–14.ConclusionsChildren, especially those aged 0–4, are much less likely to be sputum smear positive than adults. National TB programs relying on sputum smear for diagnosis are at risk of under-diagnosing and underestimating the burden of TB in children.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1617-9) contains supplementary material, which is available to authorized users.

Cambodia targets malaria elimination by 2025. Rapid elimination will depend on successfully identifying and clearing malaria foci linked to forests. Expanding and maintaining universal access to early diagnosis and effective treatment remains the key to malaria control and ultimately malaria elimination in the Greater Mekong Subregion (GMS) in the foreseeable future. Mass Drug Administration (MDA) holds some promise in the rapid reduction of Plasmodium falciparum infections, but requires considerable investment of resources and time to mobilize the target communities. Furthermore, the most practical drug regimen for MDA in the GMS-three rounds of DHA/piperaquine-has lost some of its efficacy. Mass screening and treatment benefits asymptomatic P. falciparum carriers by clearing chronic infections, but in its current form holds little promise for malaria elimination. Hopes that "highly sensitive" diagnostic tests would provide substantial advances in screen and treat programmes have been shown to be misplaced. To reduce the burden on P. falciparum and Plasmodium vivax infections in people working in forested areas novel approaches to the use of malaria prophylaxis in forest workers should be explored. During an October 2019 workshop in Phnom Penh researchers and policymakers reviewed evidence of acceptability, feasibility and effectiveness of interventions to target malaria foci and interrupt P. falciparum transmission and discussed operational requirements and conditions for programmatic implementation.

Background Rapid elimination of Plasmodium falciparum malaria in Cambodia is a goal with both national and international significance. Transmission of malaria in Cambodia is limited to forest environments, and the main population at risk consists of forest-goers who rely on forest products for income or sustenance. The ideal interventions to eliminate malaria from this population are unknown. Methods In two forested regions of Cambodia, forest-goers were trained to become forest malaria workers (FMWs). In one region, FMWs performed mass screening and treatment, focal screening and treatment, and passive case detection inside the forest. In the other region, FMWs played an observational role for the first year, to inform the choice of intervention for the second year. In both forests, FMWs collected blood samples and questionnaire data from all forest-goers they encountered. Mosquito collections were performed in each forest. Results Malaria prevalence by PCR was high in the forest, with 2.3–5.0% positive for P. falciparum and 14.6–25.0% positive for Plasmodium vivax among forest-goers in each study site. In vectors, malaria prevalence ranged from 2.1% to 9.6%, but no P. falciparum was observed. Results showed poor performance of mass screening and treatment, with sensitivity of rapid diagnostic tests equal to 9.1% (95% CI 1.1%, 29.2%) for P. falciparum and 4.4% (95% CI 1.6%, 9.2%) for P. vivax. Malaria infections were observed in all demographics and throughout the studied forests, with no clear risk factors emerging. Conclusions Malaria prevalence remains high among Cambodian forest-goers, but performance of rapid diagnostic tests is poor. More adapted strategies to this population, such as intermittent preventive treatment of forest goers, should be considered.

Various forms of preventive and prophylactic antimicrobial therapies have been proposed to combat HIV (e.g. pre-exposure prophylaxis), tuberculosis (e.g. isoniazid preventive therapy) and malaria (e.g. intermittent preventive treatment). However, the potential population-level effects of preventative therapy (PT) on the prevalence of drug resistance are not well understood. PT can directly affect the rate at which resistance is acquired among those receiving PT. It can also indirectly affect resistance by altering the rate at which resistance is acquired through treatment for active disease and by modifying the level of competition between transmission of drug-resistant and drug-sensitive pathogens. We propose a general mathematical model to explore the ways in which PT can affect the long-term prevalence of drug resistance. Depending on the relative contributions of these three mechanisms, we find that increasing the level of coverage of PT may result in increases, decreases or non-monotonic changes in the overall prevalence of drug resistance. These results demonstrate the complexity of the relationship between PT and drug resistance in the population. Care should be taken when predicting population-level changes in drug resistance from small pilot studies of PT or estimates based solely on its direct effects.

Background: Madagascar has restrictive abortion laws with no explicit exception to preserve the woman's life. This study aimed to estimate the incidence of abortion in the country and examine the methods, consequences, and risk factors of these abortions. Methods: We interviewed 3179 women between September 2015 and April 2016. Women were selected from rural and urban areas of ten districts via a multistage, stratified cluster sampling survey and asked about any induced abortions within the previous 10 years. Analyses used survey weighted estimation procedures. Quasi-Poisson regression was used to estimate the incidence rate of abortions. Logistic regression models with random effects to account for the clustered sampling design were used to estimate the risk of abortion complications by abortion method, provider, and month of pregnancy, and to describe risk factors of induced abortion. Results: For 2005-2016, we estimated an incidence rate of 18.2 abortions (95% CI 14.4-23.0) per 1000 person-years among sexually active women (aged 18-49 at the time of interview). Applying a multiplier of two as used by the World Health Organization for abortion surveys suggests a true rate of 36.4 per 1000 person-year of exposure. The majority of abortions involved invasive methods such as manual or sharp curettage or insertion of objects into the genital tract. Signs of potential infection followed 29.1% (21.8-37.7%) of abortions. However, the odds of potential infection and of seeking care after abortion did not differ significantly between women who used misoprostol alone and those who used other methods. The odds of experiencing abortion were significantly higher among women who had ever used contraceptive methods compared to those who had not. However, the proportion of women with a history of abortion was significantly lower in rural districts where contraception was available from community health workers than where it was not.

Objective Extending the duration of isoniazid preventive therapy (IPT) among people living with HIV (PLHIV) may improve its effectiveness at both the individual and population level, but could also increase selective pressure in favor of isoniazid resistant tuberculosis (TB) strains. The objective of this study was to determine the relative importance of these two effects. Methods Transmission dynamic model Design We created a mathematical model of TB transmission incorporating HIV incidence and treatment, mixed strain latent TB infections, and four different phenotypes of TB drug resistance (pan-susceptible, isoniazid mono-resistant, rifampicin mono-resistant, and multi-drug resistant). We used this model to project the effects of IPT duration on the incidence of isoniazid-sensitive and -resistant TB as well as mortality among PLHIV. We evaluated the sensitivity of our baseline model, which was calibrated to data from Botswana, to different assumptions about the future trajectory of the TB epidemic. Results Our model suggests that, in the context of a declining TB epidemic such as that currently observed in Botswana, the incidence and mortality benefits of continuous IPT for PLHIV are likely to outweigh the potential resistance risks associated with long duration IPT. However, should TB epidemics fail to remain in control, as was observed during the initial emergence of HIV, the selective pressure imposed by widespread use of continuous IPT on isoniazid resistant TB incidence may erode its initial benefits. Conclusions Resistance concerns are likely insufficient to rule out use of continuous IPT when coupled with effective TB treatment, case finding, and HIV control.

Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia. We used a simple compartmental model to predict trends in malaria incidence and resistance in Cambodia from 2020–2025 assuming no changes in transmission since 2018. We assessed three scenarios: a status quo scenario with artesunate-mefloquine (ASMQ) as treatment; a triple ACT scenario with dihydroartemisinin-piperaquine (DP) plus mefloquine (MQ) as treatment; and a chemoprophylaxis scenario with ASMQ as treatment plus DP as chemoprophylaxis. We predicted MQ resistance to increase under the status quo scenario. Triple ACT treatment reversed the spread of MQ resistance, but had no impact on overall malaria incidence. Joint MQ-PPQ resistance declined under the status quo scenario for the baseline parameter set and most sensitivity analyses. Compared to the status quo, triple ACT treatment limited spread of MQ resistance but also slowed declines in PPQ resistance in some sensitivity analyses. The chemoprophylaxis scenario decreased malaria incidence, but increased the spread of strains resistant to both MQ and PPQ; both effects began to reverse after the intervention was removed. We conclude that triple ACTs may limit spread of MQ resistance in the Cambodia, but would have limited impact on malaria incidence and might slow declines in PPQ resistance. Chemoprophylaxis could have greater impact on incidence but also carries higher risks of resistance. Aggressive strategies to limit transmission the GMS are needed to achieve elimination goals, but any intervention should be accompanied by monitoring for drug resistance.