Background. Pulmonary involvement in leptospirosis remains poorly recognized in regions where it is endemic, despite reports of recent outbreaks and

Although previous data indicate that the overall incidence of human leptospirosis in the Peruvian Amazon is similar in urban and rural sites, severe leptospirosis has been observed only in the urban context. As a potential explanation for this epidemiological observation, we tested the hypothesis that concentrations of more virulent Leptospira would be higher in urban than in rural environmental surface waters. A quantitative real-time PCR assay was used to compare levels of Leptospira in urban and rural environmental surface waters in sites in the Peruvian Amazon region of Iquitos. Molecular taxonomic analysis of a 1,200-bp segment of the leptospiral 16S ribosomal RNA gene was used to identify Leptospira to the species level. Pathogenic Leptospira species were found only in urban slum water sources (Fisher's exact test; p = 0.013). The concentration of pathogen-related Leptospira was higher in urban than rural water sources (~10³ leptospires/ml versus 0.5 × 10² leptospires/ml; F = 8.406, p < 0.05). Identical 16S rRNA gene sequences from Leptospira interrogans serovar Icterohaemorrhagiae were found in urban slum market area gutter water and in human isolates, suggesting a specific mode of transmission from rats to humans. In a prospective, population-based study of patients presenting with acute febrile illness, isolation of L. interrogans-related leptospires from humans was significantly associated with urban acquisition (75% of urban isolates); human isolates of other leptospiral species were associated with rural acquisition (78% of rural isolates) (chi-square analysis; p < 0.01). This distribution of human leptospiral isolates mirrored the distribution of leptospiral 16S ribosomal gene sequences in urban and rural water sources. Our findings data support the hypothesis that urban severe leptospirosis in the Peruvian Amazon is associated with higher concentrations of more pathogenic leptospires at sites of exposure and transmission. This combined quantitative and molecular taxonomical risk assessment of environmental surface waters is globally applicable for assessing risk for leptospiral infection and severe disease in leptospirosis-endemic regions.

Peru is an upper-middle-income country with wide social and regional disparities. In recent years, sustained multisectoral antipoverty programmes involving governments, political parties, and civil society have included explicit health and nutrition goals and spending increased sharply. We did a country case study with the aim of documenting Peru's progress in reproductive, maternal, neonatal, and child health from 2000-13, and explored the potential determinants. We examined the outcomes of health interventions coverage, under-5 mortality, neonatal mortality, and prevalence of under-5 stunting. We obtained data from interviews with key informants, a literature review of published and unpublished data, national censuses, and governmental reports. We obtained information on social determinants of health, including economic growth, poverty, unmet basic needs, urbanisation, women's education, water supply, fertility rates, and child nutrition from the annual national households surveys and the Peruvian Demographic and Health Surveys. We obtained national mortality data from the Interagency Group for Child Mortality Estimation, and calculated subnational rates from 11 surveys. Analyses were stratified by region, wealth quintiles, and urban or rural residence. We calculated coverage indicators for the years 2000-13, and we used the Lives Saved Tool (LiST) to estimate the effect of changes in intervention coverage and in nutritional status on mortality. From 2000 to 2013, under-5 mortality fell by 58% from 39·8 deaths per 1000 livebirths to 16·7. LiST, which was used to predict the decline in mortality arising from changes in fertility rates, water and sanitation, undernutrition, and coverage of indicators of reproductive, maternal, neonatal, and child health predicted that the under-5 mortality rate would fall from 39·8 to 28·4 per 1000 livebirths, accounting for 49·2% of the reported reduction. Neonatal mortality fell by 51% from 16·2 deaths per 1000 livebirths to 8·0. Stunting prevalence remained stable at around 30% until 2007, decreasing to 17·5% by 2013, and the composite coverage index for essential health interventions increased from 75·1% to 82·6%, with faster increases among the poor, in rural areas, and in the Andean region. Socioeconomic, urban-rural, and regional inequalities in coverage, mortality, and stunting were substantially reduced. The proportion of the population living below the poverty line reduced from 47·8% to 23·9%, women with fewer than 4 years of schooling reduced from 11·5% to 6·9%, urbanisation increased from 68·1% to 75·6%, and the total fertility rate decreased from 3·0 children per woman to 2·4. We interviewed 175 key informants and they raised the following issues: economic growth, improvement of social determinants, civil society empowerment and advocacy, out-of-health and within-health-sector changes, and sustained implementation of evidence-based, pro-poor reproductive, maternal, neonatal, and child health interventions. Peru has made substantial progress in reducing neonatal and under-5 mortality, and child stunting. This country is a good example of how a combination of political will, economic growth, broad societal participation, strategies focused on poor people, and increased spending in health and related sectors can achieve significant progress in reproductive, maternal, neonatal, and child health. The remaining challenges include continuing to address inequalities in wealth distribution, poverty, and access to basic services, especially in the Amazon and Andean rural areas. Bill & Melinda Gates Foundation.

Objectives: To conduct a systematic review of published and unpublished data from research and public health information systems on the prevalence of male-to-male sex in the total male population; as well as among men who have sex with men (MSM), data on prevalence of heterosexual activity and heterosexual unions; prevalence of condom use with male and female partners; and prevalence of HIV infection and other sexually transmitted infections (STIs). Methods: Key indicators were defined (a) among men in the general population: prevalence of sex with a man ever and last year; (b) among MSM: prevalence of heterosexual experiences ever and last year; proportion of male-female transgenders; proportion of sex workers; prevalence of HIV and other STIs, condom use in last sexual encounter; consistent condom use with men last year; never used a condom with a man. With help from key informants, study searches were conducted in Pubmed, LILLACS, institutional databases, conference records and other sources. Methodology and quality of information were assessed, and the best data available for 2003–7 were selected. Indicator estimates from each study were used to propose regional estimate ranges. Results: A total of 83 new entries were entered into the database in addition to the previous 561, totalling 644. Of these, 107 showing 2003–7 data were selected. Many new studies came from sub-Saharan Africa, portraying hidden HIV epidemics among MSM. The most frequently reported estimate was HIV infection, with high estimate ranges in most of the regions, except for Middle East and North Africa and Eastern Europe. The next most frequently reported was lifetime frequency of heterosexual sex, showing that roughly 50% of MSM ever had sex with a woman. The small number of newer studies reporting prevalence of “sex with a man in last 12 months” between 2003 and 2007, did not warrant enough new evidence to revise our 2005 size estimates for MSM populations. Conclusions: A considerable number of new studies with estimates of relevance to understanding sexual behaviour and HIV among MSM were identified, with an encouraging amount of new data coming from sub-Saharan Africa. However, limitations in the quality, utility and comparability of available information persist. At least three measures could be promoted for use in surveillance and academic studies: standardised indicators for MSM studies; standardised operational definitions of, and instructions to describe, variables; and standardised research designs and data gathering strategies. A prerequisite for this all is intense advocacy to ensure a social climate in which research into such matters is prioritised, resources are made available as needed and the human rights of MSM are respected.

HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary Without a vaccine, the only ways to halt the global HIV epidemic are prevention strategies that reduce transmission of the HIV virus. Up until recently, behavioral strategies such as condom use and reduction of sexual partners have been at the center of HIV prevention. In the past few years, several biological prevention measures have also been shown to be effective in reducing (though not completely preventing) HIV transmission. These include male circumcision, treatment for prevention (giving antiretroviral drugs to HIV-infected people, before they need it for their own health, to reduce their infectiousness) and pre-exposure prophylaxis (or PrEP), in which HIV-negative people use antiretroviral drugs to protect themselves from infection. One PrEP regimen (a daily pill containing two different antiretrovirals) has been shown in a clinical trial to reduce new infections by 44% in of men who have sex with men (MSM). In July 2012, the US Food and Drug Administration approved this PrEP regimen to reduce the risk of HIV infection in uninfected men and women who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners. The approval makes it clear that PrEP needs to be used in combination with safe sex practices. Clinical trials have shown that PrEP can reduce HIV infections among participants, but they have not examined the consequences PrEP could have at the population level. Before decision-makers can decide whether to invest in PrEP programs, they need to know about the costs and benefits at the population level. Besides the price of the drug itself, the costs include HIV testing before starting PrEP, as well as regular tests thereafter. The health benefits of reducing new HIV infections are calculated in “disability-adjusted life years” (or DALYs) averted. One DALY is equal to one year of healthy life lost. Other benefits include future savings in lifelong HIV/AIDS treatment for every person whose infection is prevented by PrEP. This study estimates the potential costs and health benefits of several hypothetical PrEP roll-out scenarios among the community of MSM in Lima, Peru. The scientists chose this community because many of the participants in the clinical trial that showed that PrEP can reduce infections came from this community, and they therefore have some knowledge on how PrEP affects HIV infection rates and behavior in this population. Because the HIV epidemic in Lima is concentrated among MSM, similar to most of Latin America and several other developed countries, the results might also be relevant for the evaluation of PrEP in other places. For their scenarios, the researchers looked at “high coverage” and “low coverage” scenarios, in which 20% and 5% of uninfected individuals use PrEP, respectively. They also divided the MSM community into those at lower risk of becoming infected and those at higher risk. The latter group consisted of transwomen at higher risk (transsexuals and transvestites with many sexual partners) and male sex workers. In a “uniform coverage” scenario, PrEP is equally distributed among all MSM. “Prioritized scenarios” cover transwomen at higher risk and sex workers preferentially. Two additional important factors for the estimated benefits are treatment adherence (i.e., whether people take the pills they have been prescribed faithfully over long periods of time even though they are not sick) and changes in risk behavior (i.e., whether the perceived protection provided by PrEP leads to more unprotected sex). The cost estimates for PrEP included the costs of the drug itself and HIV tests prior to PrEP prescription and at three-month intervals thereafter, as well as outreach and counseling services and condom and lubricant promotion and provision. To judge whether under the various scenarios PrEP is cost-effective, the researchers applied two commonly used but different cost-effectiveness thresholds. The World Health Organization's WHO-CHOICE initiative considers an intervention cost-effective if its cost is less than three times the gross domestic product (GDP) per capita per DALY averted. For Peru, this means an intervention should cost less than US$16,302 per DALY. The World Bank has more stringent criteria: it considers an intervention cost-effective for a middle-income country like Peru if it costs less than US$500 per DALY averted. The researchers estimate that PrEP is cost-effective in Lima's MSM population for most scenarios by WHO-CHOICE guidelines. Only scenarios that prioritize PrEP to those most likely to become infected (i.e., transwomen at higher risk and sex workers) are cost-effective (and only barely) by the more stringent World Bank criteria. If the savings on antiretroviral drugs to treat people with HIV (those who would have become infected without PrEP) are included in the calculation, most scenarios become cost-effective, even under World Bank criteria. The most cost-effective scenario, namely, having a modest coverage of 5%, prioritizing PrEP to transwomen at higher risk and sex workers, and assuming fairly high adherence levels among PrEP recipients, is estimated to avert about 8% of new infections among this community over ten years. These findings suggest that under some circumstances, PrEP could be a cost-effective tool to reduce new HIV infections. However, as the researchers discuss, PrEP is expensive and only partly effective. Moreover, its effectiveness depends on two behavioral factors—adherence to a strict drug regimen and continued practicing of safe sex—both of which remain hard to predict. As a consequence, PrEP alone is not a valid strategy to prevent new HIV infections. It needs instead to be considered as one of several available tools. If and when PrEP is chosen as part of an integrated prevention strategy will depend on the specific target population, the overall funds available, and how well its cost-effectiveness compares with other prevention measures. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001323.