Inaccurate Diagnosis of HIV-1 Group M and O Is a Key Challenge for Ongoing Universal Access to Antiretroviral Treatment and HIV Prevention in Cameroon

Background

Increased access to HIV testing is essential in working towards universal access to HIV prevention and treatment in resource-limited countries. We here evaluated currently used HIV diagnostic tests and algorithms in Cameroon for their ability to correctly identify HIV infections.

Methods

We estimated sensitivity, specificity, and positive and negative predictive values of 5 rapid/simple tests, of which 3 were used by the national program, and 2 fourth generation ELISAs. The reference panel included 500 locally collected samples; 187 HIV -1 M, 10 HIV-1 O, 259 HIV negative and 44 HIV indeterminate plasmas.

Results

None of the 5 rapid assays and only 1 ELISA reached the current WHO/UNAIDS recommendations on performance of HIV tests of at least 99% sensitivity and 98% specificity. Overall, sensitivities ranged between 94.1% and 100%, while specificities were 88.0% to 98.8%. The combination of all assays generated up to 9% of samples with indeterminate HIV status, because they reacted discordantly with at least one of the different tests. Including HIV indeterminate samples in test efficiency calculations significantly decreased specificities to a range from 77.9% to 98.0%. Finally, two rapid assays failed to detect all HIV-1 group O variants tested, with one rapid test detecting only 2 out of 10 group O specimens.

Conclusion

In the era of ART scaling-up in Africa, significant proportions of false positive but also false negative results are still observed with HIV screening tests commonly used in Africa, resulting in inadequate treatment and prevention strategies. Depending on tests or algorithms used, up to 6% of HIV-1 M and 80% of HIV-1 O infected patients in Cameroon do not receive ART and adequate counseling to prevent further transmission due to low sensitivities. Also, the use of tests with low specificities could imply inclusion of up to 12% HIV negative people in ART programs and increase budgets in addition to inconveniences caused to patients.     

Determining the impact of community awareness-raising activities on the prevention of malaria transmission in Palawan,the Philippines

Palawan has the highest malaria endemicity in the Philippines, and malaria remains a major health burden in the region. In 1999, 344 microscopists were trained in Palawan. This allowed for early diagnosis and prompt treatment throughout the island. To take a significant step toward the elimination of malaria on the island, microscopists implemented community awareness-raising activities aimed at preventing transmission of malaria. The objective of the present study was to determine the impact of these activities on the self-implemented preventive measures against malaria by the ex-patients of the microscopists. Structured interviews were carried out from January to February in 2012, in 20 remote malaria-endemic villages throughout Palawan. In total, 141 ex-patients who had previously been diagnosed malaria-positive by the microscopists, volunteered to participate in the present study. Structural equation modeling was conducted to determine factors associated with self-implemented preventive measures against malaria, which included: (1) place of residence; (2) socio-demographic characteristics; (3) knowledge on malaria; (4) participation in community awareness-raising activities for malaria prevention; and (5) satisfaction with microscopists. Structural equation modeling identified six significant factors independently associated with self-implemented preventive measures against malaria; ethnicity, knowledge on malaria transmission, knowledge on vector species, knowledge on vector's most active time, participation in awareness-raising activities for malaria prevention by microscopists, and satisfaction with microscopists. Tagalog ethnicity (the predominant ethnic group) was positively related to better self-implemented preventive measures. In conclusion, aside from providing early diagnosis and treatment, microscopists played a significant role in self-implemented preventive measures against malaria. The strengthening of awareness-raising activities by microscopists was suggested to be an effective strategy for reducing malaria re-infection in Palawan. These activities should be strengthened to improve preventive measures implemented by ex-patients traveling to mountain areas and to enhance the knowledge on malaria transmission particularly among indigenous residents.     

Allelic diversity in the merozoite surface protein 1 gene of Plasmodium falciparum on Palawan Island, the Philippines

Allelic diversity of the Plasmodium falciparum merozoite surface protein 1 gene (msp1) is mainly generated by meiotic recombination at the mosquito stage. We investigated recombination-based allelic diversity of msp1 in a P. falciparum population from Palawan Island, the Philippines, where malaria transmission is moderate. We identified the 5' recombinant types, 3' sequence types and msp1 haplotypes (unique combinations of 5' recombinant type and 3' sequence type), and compared them with those of P. falciparum from the Solomon Islands, where malaria transmission is high. The mean number of 5' recombinant types per patient in Palawan was 1.44, which is comparable to the number for the Solomon Islands (1.41). The Palawan parasite population had 15 msp1 haplotypes, whereas the Solomon Islands population had only 8 haplotypes. The Palawan population showed strong linkage disequilibrium between polymorphic blocks/sites within msp1, which is comparable to the results for the Solomon Islands. These findings support our hypothesis that the extent of allelic diversity of msp1 is determined not only by the transmission intensity but also by the number of msp1 alleles prevalent in the local parasite population and the extent of mixed-allele infections. Contribution of a high prevalence of the chloroquine (CQ)-sensitive allele of P. falciparum CQ resistance transporter (pfcrt) to the relatively high msp1 diversity in the Palawan population is discussed.     

Hidden Drug Resistant HIV to Emerge in the Era of Universal Treatment Access in Southeast Asia

Background

Universal access to first-line antiretroviral therapy (ART) for HIV infection is becoming more of a reality in most low and middle income countries in Asia. However, second-line therapies are relatively scarce.

Methods and Findings

We developed a mathematical model of an HIV epidemic in a Southeast Asian setting and used it to forecast the impact of treatment plans, without second-line options, on the potential degree of acquisition and transmission of drug resistant HIV strains. We show that after 10 years of universal treatment access, up to 20% of treatment-naïve individuals with HIV may have drug-resistant strains but it depends on the relative fitness of viral strains.

Conclusions

If viral load testing of people on ART is carried out on a yearly basis and virological failure leads to effective second-line therapy, then transmitted drug resistance could be reduced by 80%. Greater efforts are required for minimizing first-line failure, to detect virological failure earlier, and to procure access to second-line therapies.     

The use of non-wood forest products by migrants in a new settlement: experiences of a Visayan community in Palawan, Philippines

Background

More than twelve temperate-inhabitant Mexican ethnic groups are considered to be mycophilic and to have extensive traditional mycological knowledge. In contrast, inhabitants of tropical lands have been studied only superficially and their mycological knowledge is less well known. In this paper, we report the results of an ethnomycological research in markets of a wide area of the Mexican tropics. Our aims were to describe the dynamics related to the traditional selling process of wild mushrooms and to determine the tendencies of informants toward mushrooms (mycophily vs. mycophoby).

Methods

We visited 25 markets of 12 different settlements in the states of Oaxaca, Tabasco and Veracruz and collected information by participant observation as well as by 291 non-structured and semi-structured interviews.

Results

Mushroom selling was observed in four towns in Oaxaca and in two in Tabasco. Women represented 81.82% of sellers, while indigenous people (Chinantecos, Chontales, Ch'oles and Zoques) comprised 68.18%. Mushroom commercialization took place in secondary mobile markets and only in peasant stands. Mushroom collectors gather the resource in places with secondary vegetation, farmed areas and cattle fields. Because of land tenure restrictions mushroom sellers did not normally collect mushrooms themselves. In Oaxaca, we observed economic dynamics not based on capitalism, such as exchange, reciprocity and barter.

Conclusion

The sale of some wild edible mushrooms, the large amounts of commercialization of Schizophyllum commune, the complicated intermediary process, as well as the insertion of mushrooms into different informal economic practices are all evidence of an existent mycophily in a sector of the population of this region of the Mexican tropics. Among our informants, urban mestizo people were mycophobic, rural mestizo people were non-mycophilic and indigenous people were true mycophilic.     

The freshwater crab fauna (Crustacea: Brachyura) of the Philippines. V. On a new genus and species of potamid from Palawan island, Philippines

A new genus and new species of terrestrial potamid crab ( Carpomon pomulum) is described from the island of Palawan in the Philippines. This new genus can easily be distinguished from all other Philippine potamids in its smooth and inflated carapace, no trace of an epibranchial tooth, extremely low postorbital cristae, and stout and twisted male first gonopod. This revised version was published online in July 2006 with corrections to the Cover Date.     

Subsistence strategies of an indigenous minority in the Philippines: Nonwood forest product use by the Tagbanua of Narra, Palawan

Indigenous people, such as the Tagbanua of Palawan Island in the Philippines, are often considered to be experienced and responsible users of natural resources. The Tagbanua have traditionally been involved in the collection of nonwood forest products (NWFPs) both for trade and for subsistence purposes. The proximity of many Tagbanua communities to the forest allows them easy access to NWFPs, although various restrictions, such as distance from markets, legal land issues, and lack of formal education, prevent them from receiving more favorable earnings from the sale of NWFPs. Similarly, increasing access to manufactured products also lessens dependence on NWFPs for food, medicine, and housing purposes, although small incomes prevent extensive conversion to the use of purchased goods. The knowledge and current subsistence-level use of NWFPs by the Tagbanua from the settlement of Boong are described and discussed.     

How Patients Take Malaria Treatment: A Systematic Review of the Literature on Adherence to Antimalarial Drugs

Background

High levels of patient adherence to antimalarial treatment are important in ensuring drug effectiveness. To achieve this goal, it is important to understand levels of patient adherence, and the range of study designs and methodological challenges involved in measuring adherence and interpreting results. Since antimalarial adherence was reviewed in 2004, there has been a major expansion in the use of artemisinin-based combination therapies (ACTs) in the public sector, as well as initiatives to make them more widely accessible through community health workers and private retailers. These changes and the large number of recent adherence studies raise the need for an updated review on this topic.

Objective

We conducted a systematic review of studies reporting quantitative results on patient adherence to antimalarials obtained for treatment.

Results

The 55 studies identified reported extensive variation in patient adherence to antimalarials, with many studies reporting very high adherence (90–100%) and others finding adherence of less than 50%. We identified five overarching approaches to assessing adherence based on the definition of adherence and the methods used to measure it. Overall, there was no clear pattern in adherence results by approach. However, adherence tended to be higher among studies where informed consent was collected at the time of obtaining the drug, where patient consultations were directly observed by research staff, and where a diagnostic test was obtained.

Conclusion

Variations in reported adherence may reflect factors related to patient characteristics and the nature of their consultation with the provider, as well as methodological variations such as interaction between the research team and patients before and during the treatment. Future studies can benefit from an awareness of the impact of study procedures on adherence outcomes, and the identification of improved measurement methods less dependent on self-report.     

Voriconazole Proves Effective in Long-Term Treatment of a Cerebral Cryptococcoma in a Chronic Nephropathic HIV-Negative Patient,after Fluconazole Failure

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary-secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.     

Urzymology: Experimental Access to a Key Transition in the Appearance of Enzymes

Urzymes are catalysts derived from invariant cores of protein superfamilies. Urzymes from both aminoacyl-tRNA synthetase classes possess sophisticated catalytic mechanisms: pre-steady state bursts, significant transition-state stabilization of both amino acid activation, and tRNA acylation. However, they have insufficient specificity to ensure a fully developed genetic code, suggesting that they participated in synthesizing statistical proteins. They represent a robust experimental platform from which to articulate and test hypotheses both about their own ancestors and about how they, in turn, evolved into modern enzymes. They help reshape numerous paradigms from the RNA World hypothesis to protein structure databases and allostery.     

MC-12, an Annexin A1-Based Peptide, Is Effective in the Treatment of Experimental Colitis

Annexin A1 (ANXA1) inhibits NF-κB, a key regulator of inflammation, the common pathophysiological mechanism of inflammatory bowel diseases (IBD). MC-12, an ANXA1-based tripeptide, suppresses NF-κB activation. Here, we determined the efficacy of MC-12 in the control of IBD. Mice with colitis induced by dextran sodium sulfate (DSS) or 2,4,6-trinitro benzene sulfonic acid (TNBS) were treated with various doses of MC-12 administered intraperitoneally, orally or intrarectally. We determined colon length and the histological score of colitis, and assayed: in colon tissue the levels of TNF-α, IFN-γ, IL-1β, IL-6 and IL-10 by RT-PCR; prostaglandin E(2) (PGE(2)), cytoplasmic phospholipase A(2) (cPLA(2)) and myeloperoxidase by immunoassay; and COX-2 and NF- κB by immunohistochemistry; and in serum the levels of various cytokines by immunoassay. In both models MC-12: reversed dose-dependently colonic inflammation; inhibited by up to 47% myeloperoxidase activity; had a minimal effect on cytoplasmic phospholipase A(2); reduced significantly the induced levels of TNF-α, IFN-γ, IL-1β, IL-6 and IL-10, returning them to baseline. DSS and TNBS markedly activated NF-κB in colonic epithelial cells and MC-12 decreased this effect by 85.8% and 72.5%, respectively. MC-12 had a similar effect in cultured NCM460 normal colon epithelial cells. Finally, MC-12 suppressed the induction of COX-2 expression, the level of PGE(2) in the colon and PGE(2) metabolite in serum. In conclusion, MC-12, representing a novel class of short peptide inhibitors of NF-κB, has a strong effect against colitis in two preclinical models recapitulating features of human IBD. Its mechanism of action is complex and includes pronounced inhibition of NF-κB. MC-12 merits further development as an agent for the control of IBD.     

Anemia of Inflammation Is Related to Cognitive Impairment among Children in Leyte,The Philippines

Background

Many studies have addressed the relationship between iron deficiency anemia (IDA) and cognitive impairment, but none have evaluated the role of non-iron deficiency anemia (NIDA). One of the main causes of NIDA in developing countries is AI, largely due to infectious diseases, whereby iron is shunted away from bio-available forms to storage forms, making it less accessible for use by host tissues. The objective of this study was to determine the effect of NIDA, due largely to AI in this context, on cognitive function after adjustment for potential confounders.

Methodology

This cross-sectional study was conducted in Leyte, The Philippines among 322 children ages 7–18 years. Blood samples were collected and analyzed at the time of cognition testing. Three stool samples were collected and evaluated by the Kato Katz method for quantitative assessment for Schistosoma japonicum and geo-helminth infection. Socio-economic status (SES) was evaluated by survey. Linear regression models were used to quantify the adjusted relationship between performance in different cognitive domains and both IDA and NIDA.

Principal Findings

After adjusting for age, sex, SES and nutritional status, children in the NIDA had lower scores on the PNIT (P = <0.05) and the WRAML memory domain (P<0.05) compared to children in the non-anemic group. Children in the IDA had lower performance on the PNIT compared to the non-anemic group after controlling for potential confounders (P<0.05).

Conclusions

NIDA, predominantly due to AI in this context, was related to lower performance on two tests of cognitive function. This is likely due to decreased delivery of iron to host tissues in this context, including the CNS.     

Larvae and a new species of Ancyronyx Erichson, 1847 (Insecta, Coleoptera, Elmidae) from Palawan, Philippines, using DNA sequences for the assignment of the developmental stages

Ancyronyx montanussp. n. is described based on adults and larvae, matched using their cox1 DNA sequence data. Larvae of six additional species of Ancyronyx Erichson, 1847 were also described here for the first time, aided by cox1 or cob data: Ancyronyx helgeschneideri Freitag & J?ch, 2007, Ancyronyx minerva Freitag & J?ch, 2007, Ancyronyx patrolus Freitag & J?ch, 2007, Ancyronyx procerus J?ch, 1994, Ancyronyx punkti Freitag & J?ch, 2007, Ancyronyx pseudopatrolus Freitag & J?ch, 2007. Ancyronyx procerus is newly recorded from the Philippines by a larval specimen from Busuanga island. The new species and larval stages are described in detail and illustrated by digital and SEM images. A key to the Ancyronyx larvae of Palawan and an updated checklist of Philippine Ancyronyx is provided.     

Knowledge,Attitudes and Perceptions Regarding Endemic Vivax Malaria in Inhabitants and Patients in Two Cities of Northern Gyeonggi-do,Korea, 2020

An understanding of the knowledges, attitudes and perceptions of different populations is key for public health policy makers. Here, a survey was performed on knowledge, attitudes, and perceptions about malaria diagnosis, prevention, control, and treatment. The 407 survey participants included both uninfected inhabitants and patients from 2 cities (Gimpo- and Paju-si) of Northern Gyeonggi-do, known as high-risk areas for vivax malaria. We used community-based study design and non-probability sampling method using the primary data. Association between variables were tested using χ²-tests. In general, the information on malaria reported by the participants in this study was unsystematic and included inaccurate details. The knowledge of malaria symptoms, identified as headache, chills and fever, was high, but the surveyed community lacks knowledge of the specific medications used for malaria treatment, with a large number of respondents having no knowledge of any form of medication. Survey questions with high correct answer rates included questions about easy treatment of malaria in Korea, the high daytime activity of malaria-borne mosquitoes, and the infection risk posed by outdoor activities. However, a large portion of the respondents was unable to provide simple medical and biological information about the disease. This study aimed to comprehensively evaluate the knowledge, attitude, and practical behavior of the surveyed community with respect to malaria and the implications reported here could be applicable to other malaria endemic areas in Korea.     

From Synovial Tissue to Peripheral Blood: Myeloid Related Protein 8/14 Is a Sensitive Biomarker for Effective Treatment in Early Drug Development in Patients with Rheumatoid Arthritis

Objective

The change in number of CD68-positive sublining macrophages in serial synovial biopsies has been successfully used to discriminate on the group level between effective and ineffective treatment during early drug development in rheumatoid arthritis (RA) patients. Measurement of a soluble biomarker would clearly have practical advantages. Therefore, we investigated the sensitivity to change of myeloid related protein (MRP)8/14 in serum.

Methods

139 RA patients who received known effective biologics (infliximab, adalimumab and rituximab) and 28 RA patients who received placebo/ineffective therapies were included. MRP8/14 levels were analyzed in baseline and follow-up serum samples and the standardized response mean (SRM) was calculated to determine the sensitivity to change of MRP8/14 in comparison to C-reactive protein (CRP) levels and the disease activity score evaluated in 28 joints (DAS28).

Results

In patients treated with effective treatment, the SRM for MRP8/14 was moderate (0.56), but in patients treated with placebo/ineffective treatment the SRM was 0.06, suggesting that this biomarker is perhaps not susceptible to placebo effects in proof-of-concept studies of relatively short duration. In contrast, the SRM for DAS28 was high for effective treatment (1.07), but also moderate for ineffective treatment (0.58), representing the placebo effect. The SRM for CRP was low in the effective (0.33) and ineffective (0.23) treatment groups.

Conclusion

These data support the notion that quantification of changes in MRP8/14 serum levels could be used to predict potential efficacy of novel antirheumatic drugs in an early stage of drug development. A positive result would support the rationale for larger, conventional clinical trials to determine whether the effects are clinically relevant.     

Promoting Help-Seeking in Response to Symptoms amongst Primary Care Patients at High Risk of Lung Cancer: A Mixed Method Study

BackgroundLung cancer symptoms are vague and difficult to detect. Interventions are needed to promote early diagnosis, however health services are already pressurised. This study explored symptomology and help-seeking behaviours of primary care patients at ‘high-risk’ of lung cancer (≥50 years old, recent smoking history), to inform targeted interventions.MethodsMixed method study with patients at eight general practitioner (GP) practices across south England. Study incorporated: postal symptom questionnaire; clinical records review of participant consultation behaviour 12 months pre- and post-questionnaire; qualitative participant interviews (n = 38) with a purposive sample.ResultsA small, clinically relevant group (n = 61/908, 6.7%) of primary care patients was identified who, despite reporting potential symptoms of lung cancer in questionnaires, had not consulted a GP ≥12 months. Of nine symptoms associated with lung cancer, 53.4% (629/1172) of total respondents reported ≥1, and 35% (411/1172) reported ≥2. Most participants (77.3%, n = 686/908) had comorbid conditions; 47.8%, (n = 414/908) associated with chest and respiratory symptoms. Participant consulting behaviour significantly increased in the 3-month period following questionnaire completion compared with the previous 3-month period (p = .002), indicating questionnaires impacted upon consulting behaviour. Symptomatic non-consulters were predominantly younger, employed, with higher multiple deprivation scores than their GP practice mean. Of symptomatic non-consulters, 30% (18/61) consulted ≤1 month post-questionnaire, with comorbidities subsequently diagnosed for five participants. Interviews (n = 39) indicated three overarching differences between the views of consulting and non-consulting participants: concern over wasting their own as well as GP time; high tolerance threshold for symptoms; a greater tendency to self-manage symptoms.ConclusionsThis first study to examine symptoms and consulting behaviour amongst a primary care population at ‘high- risk’ of lung cancer, found symptomatic patients who rarely consult GPs, might respond to a targeted symptom elicitation intervention. Such GP-based interventions may promote early diagnosis of lung cancer or other comorbidities, without burdening already pressurised services.