HIV decline in Zimbabwe due to reductions in risky sex? Evidence from a comprehensive epidemiological review.

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Protected Areas in Tropical Africa: Assessing Threats and Conservation Activities

Numerous protected areas (PAs) have been created in Africa to safeguard wildlife and other natural resources. However, significant threats from anthropogenic activities and decline of wildlife populations persist, while conservation efforts in most PAs are still minimal. We assessed the impact level of the most common threats to wildlife within PAs in tropical Africa and the relationship of conservation activities with threat impact level. We collated data on 98 PAs with tropical forest cover from 15 countries across West, Central and East Africa. For this, we assembled information about local threats as well as conservation activities from published and unpublished literature, and questionnaires sent to long-term field workers. We constructed general linear models to test the significance of specific conservation activities in relation to the threat impact level. Subsistence and commercial hunting were identified as the most common direct threats to wildlife and found to be most prevalent in West and Central Africa. Agriculture and logging represented the most common indirect threats, and were most prevalent in West Africa. We found that the long-term presence of conservation activities (such as law enforcement, research and tourism) was associated with lower threat impact levels. Our results highlight deficiencies in the management effectiveness of several PAs across tropical Africa, and conclude that PA management should invest more into conservation activities with long-term duration.Additional co-authors: Jef Dupain, Atanga Ekobo, Manasseh Eno-Nku, Gilles Etoga, Takeshi Furuichi, Sylvain Gatti, Andrea Ghiurghi, Chie Hashimoto, John A. Hart, Josephine Head, Martin Hega, Ilka Herbinger, Thurston C. Hicks, Lars H. Holbech, Bas Huijbregts, Hjalmar S. Kühl, Inaoyom Imong, Stephane Le-Duc Yeno, Joshua Linder, Phil Marshall, Peter Minasoma Lero, David Morgan, Leonard Mubalama, Paul K. N'Goran, Aaron Nicholas, Stuart Nixon, Emmanuelle Normand, Leonidas Nziguyimpa, Zacharie Nzooh-Dongmo, Richard Ofori-Amanfo, Babafemi G. Ogunjemite, Charles-Albert Petre, Hugo J. Rainey, Sebastien Regnaut, Orume Robinson, Aaron Rundus, Crickette M. Sanz, David Tiku Okon, Angelique Todd, Ymke Warren, Volker Somme

Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed. RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS. CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further

The Angiotensin Converting Enzyme Insertion/Deletion polymorphism is not associated with an increased risk of death or bronchopulmonary dysplasia in ventilated very low birth weight infants

BACKGROUND: The ACE gene contains a polymorphism consisting of either the presence (insertion, I) or absence (deletion, D) of a 287 bp alu repeat in intron 16. The D allele is associated with increased ACE activity in both tissue and plasma. The DD genotype is associated with risk of developing ARDS and mortality. The frequency of the D allele is higher in patients with pulmonary fibrosis, sarcoidosis and berylliosis. The role of this polymorphism has not been studied in the development of BPD in the premature newborn. METHODS: ACE I/D genotype was determined in 245 (194 African-American, 47 Caucasian and 4 Hispanic) mechanically ventilated infants weighing less than 1250 grams at birth and compared to outcome (death and/or development of BPD). RESULTS: The incidence of the D allele in the study population was 0.58. Eighty-eight (35.9%) infants were homozygous DD, 107 (43.7%) were heterozygous ID and 50 (20.4%) were homozygous II. There were no significant differences between genotype groups with respect to ethnic origin, birth weight, gestation, or gender. There was no effect of the ACE I/D polymorphism on mortality or development of BPD (O(2 )on 28 days or 36 weeks PCA). Secondary outcomes (intraventricular hemorrhage and periventricular leukomalacia) similarly were not influenced by the ACE ID polymorphism. CONCLUSIONS: The ACE I/D polymorphism does not significantly influence the development of BPD in ventilated infants less than 1250 grams

Non-Native R1 Substitution in the S4 Domain Uniquely Alters Kv4.3 Channel Gating

The S4 transmembrane domain in Shaker (Kv1) voltage-sensitive potassium channels has four basic residues (R1–R4) that are responsible for carrying the majority of gating charge. In Kv4 channels, however, R1 is replaced by a neutral valine at position 287. Among other differences, Kv4 channels display prominent closed state inactivation, a mechanism which is minimal in Shaker. To determine if the absence of R1 is responsible for important variation in gating characteristics between the two channel types, we introduced the V287R mutant into Kv4.3 and analyzed its effects on several voltage sensitive gating transitions. We found that the mutant increased the voltage sensitivity of steady-state activation and altered the kinetics of activation and deactivation processes. Although the kinetics of macroscopic inactivation were minimally affected, the characteristics of closed-state inactivation and recovery from open and closed inactivated states were significantly altered. The absence of R1 can only partially account for differences in the effective voltage sensitivity of gating between Shaker and Kv4.3. These results suggest that the S4 domain serves an important functional role in Kv4 channel activation and deactivation processes, and also those of closed-state inactivation and recovery

Lost opportunities in HIV prevention: programmes miss places where exposures are highest

Background: Efforts at HIV prevention that focus on high risk places might be more effective and less stigmatizing than those targeting high risk groups. The objective of the present study was to assess risk behaviour patterns, signs of current preventive interventions and apparent gaps in places where the risk of HIV transmission is high and in communities with high HIV prevalence. Methods: The PLACE method was used to collect data. Inhabitants of selected communities in Lusaka and Livingstone were interviewed about where people met new sexual partners. Signs of HIV preventive activities in these places were recorded. At selected venues, people were interviewed about their sexual behaviour. Peer educators and staff of NGOs were also interviewed. Results: The places identified were mostly bars, restaurants or sherbeens, and fewer than 20% reported any HIV preventive activity such as meetings, pamphlets or posters. In 43% of places in Livingstone and 26% in Lusaka, condoms were never available. There were few active peer educators. Among the 432 persons in Lusaka and 676 in Livingstone who were invited for interview about sexual behaviour, consistent condom use was relatively high in Lusaka (77%) but low in Livingstone (44% of men and 34% of women). Having no condom available was the most common reason for not using one. Condom use in Livingstone was higher among individuals socializing in places where condoms always were available. Conclusion: In the places studied we found a high prevalence of behaviours with a high potential for HIV transmission but few signs of HIV preventive interventions. Covering the gaps in prevention in these high exposure places should be given the highest priority

Prevalence and risk factors for HIV-1 infection in rural Kilimanjaro region of Tanzania: Implications for prevention and treatment

BACKGROUND: Variability in stages of the HIV-1 epidemic and hence HIV-1 prevalence exists in different areas in sub-Saharan Africa. The purpose of this study was to investigate the magnitude of HIV-1 infection and identify HIV-1 risk factors that may help to develop preventive strategies in rural Kilimanjaro, Tanzania. METHODS: A cross-sectional study was conducted between March and May of 2005 involving all individuals aged between 15–44 years having an address in Oria Village. All eligible individuals were registered and invited to participate. Participants were interviewed regarding their demographic characteristics, sexual behaviors, and medical history. Following a pre-test counseling, participants were offered an HIV test. RESULTS: Of the 2 093 eligible individuals, 1 528 (73.0%) participated. The overall age and sex adjusted HIV-1 prevalence was 5.6%. Women had 2.5 times higher prevalence (8.0% vs. 3.2%) as compared to men. The age group 25–44 years, marriage, separation and low education were associated with higher risk of HIV-1 infection for both sexes. HIV-1 infection was significantly associated with >2 sexual partners in the past 12 months (women: Adjusted odds ratio [AOR], 2.5 (95%CI: 1.3–4.7), and past 5 years, [(men: AOR, 2.2 (95%CI:1.2–5.6); women: AOR, 2.5 (95%CI: 1.4–4.0)], unprotected casual sex (men: AOR,1.8 95%CI: 1.2–5.8), bottled alcohol (Men: AOR, 5.9 (95%CI:1.7–20.1) and local brew (men: AOR, 3.7 (95%CI: 1.5–9.2). Other factors included treatment for genital ulcers and genital discharge in the past 1 month. Health-related complaints were more common among HIV-1 seropositive as compared to seronegative participants and predicted the presence of HIV-1 infection. CONCLUSION: HIV-1 infection was highly prevalent in this population. As compared to our previous findings, a shift of the epidemic from a younger to an older age group and from educated to uneducated individuals was observed. Women and married or separated individuals remained at higher risk of infection. To prevent further escalation of the HIV epidemic, efforts to scale up HIV prevention programmes addressing females, people with low education, lower age at marriage, alcohol consumption, condom use and multiple sexual partners for all age groups remains a top priority. Care and treatment are urgently needed for those infected in rural areas

Efficacy of Structural-Level Condom Distribution Interventions: A Meta-Analysis of U.S. and International Studies, 1998–2007

This systematic review examines the overall efficacy of U.S. and international-based structural-level condom distribution interventions (SLCDIs) on HIV risk behaviors and STIs and identifies factors associated with intervention efficacy. A comprehensive literature search of studies published from January 1988 through September 2007 yielded 21 relevant studies. Significant intervention effects were found for the following outcomes: condom use, condom acquisition/condom carrying, delayed sexual initiation among youth, and reduced incident STIs. The stratified analyses for condom use indicated that interventions were efficacious for various groups (e.g., youth, adults, males, commercial sex workers, clinic populations, and populations in areas with high STI incidence). Interventions increasing the availability of or accessibility to condoms or including additional individual, small-group or community-level components along with condom distribution were shown to be efficacious in increasing condom use behaviors. This review suggests that SLCDIs provide an efficacious means of HIV/STI prevention

The impact of HIV-1 on the malaria parasite biomass in adults in sub-Saharan Africa contributes to the emergence of antimalarial drug resistance

Background. HIV-related immune-suppression increases the risk of malaria (infection, disease and treatment failure) and probably the circulating parasite biomass, favoring the emergence of drug resistance parasites. Methods. The additional malaria parasite biomass related to HIV-1 co-infection in sub-Saharan Africa was estimated by a mathematical model. Parasite biomass was computed as the incidence rate of clinical malaria episodes multiplied by the number of parasites circulating in the peripheral blood of patients at the time symptoms appear. A mathematical model estimated the influence of HIV-1 infection on parasite density in clinical malaria by country and by age group, malaria transmission intensity and urban/rural area. In a multivariate sensitivity analysis, 95% confidence intervals (CIs) were calculated using the Monte Carlo simulation. Results. The model shows that in 2005 HIV-1 increased the overall malaria parasite biomass by 18.0% (95%CI: 11.6-26.9). The largest relative increase (134.9-243.9%) was found in southern Africa where HIV-1 prevalence is the highest and malaria transmission unstable. The largest absolute increase was found in Zambia, Malawi, the Central African Republic and Mozambique, where both malaria and HIV are highly endemic. A univariate sensitivity analysis shows that estimates are sensitive to the magnitude of the impact of HIV-1 infection on the malaria incidence rates and associated parasite densities. Conclusion. The HIV-1 epidemic by increasing the malaria parasite biomass in sub-Saharan Africa may also increase the emergence of antimalarial drug resistance, potentially affecting the health of the whole population in countries endemic for both HIV-1 and malaria