Evaluation of care and treatment clinics using a four-year retrospective cohort of patients receiving anti-retroviral therapy in Mbeya Region, Tanzania

Evaluations of sub-national anti-retroviral therapy (ART) programmes’ performance are important to support regional programme planning and epidemic response. We constructed a four-year retrospective cohort of clients from 10 care and treatment clinics (CTC) in the Mbeya region of Tanzania using routinely collected data from patients initiating ART between January 1, 2008 and March 31, 2012. Our primary outcomes were mortality rate and lost to follow up. We calculated ART coverage based on regional prevalence estimates and used medical cards, drug registers and quarterly reports to assess data quality. We enrolled 17,813 participants into the cohort. More patients initiated ART at WHO stages 3 (58.9%), and at CD4 cell counts between 50-199 cells/µl (56%). The proportion of patients initiating ARTs at a CD4 counts <50 cells/µl decreased from 40.7% in 2008 to 33.8% in 2012 (p-value <0.001). A total of 10,155 (57.0%) patients were lost to follow up (LTFU) during the 4 years of follow up; 59.2% were female. The overall mortality rate was 17.8 per 1000 person years; the six-month mortality was 6.2 per 1000 person years. The risk of mortality for patients at WHO stage III and IV was more than twice as high (hazard ratio [HR] 2.15; 95% confidence interval [CI], 1.05-4.39 and HR 2.29; 95% CI, 1.39-6.37, respectively) as compared to stage I and II. Those patients initiating ART with CD4 cell count between 50 and 199 cells/µl had significantly lower hazard of death compared to those initiating ART with CD4 cells counts <50 cells/µl (HR 0.51, 95% CI 0.34-0.78). In conclusion, during the study, a high proportion of patients were lost to follow up, and the majority of them were female. Most patients initiated ARTs at lower CD4 count (<200 cells/mm3) and at WHO stages III and IV, and they had higher risk of mortality compared to those initiated at higher CD4 counts and WHO stage I and II. Emphasis needs to be placed on strategies of early diagnosis of HIV infection, prompt initiation of ART, and support for ART adherence to minimise lost to follow up

Comparative performance of three experimental hut designs for measuring malaria vector responses to insecticides in Tanzania.

BACKGROUND: Experimental huts are simplified, standardized representations of human habitations that provide model systems to evaluate insecticides used in indoor residual spray (IRS) and long-lasting insecticidal nets (LLINs) to kill disease vectors. Hut volume, construction materials and size of entry points impact mosquito entry and exposure to insecticides. The performance of three standard experimental hut designs was compared to evaluate insecticide used in LLINs. METHODS: Field studies were conducted at the World Health Organization Pesticide Evaluation Scheme (WHOPES) testing site in Muheza, Tanzania. Three East African huts, three West African huts, and three Ifakara huts were compared using Olyset(®) and Permanet 2.0(®) versus untreated nets as a control. Outcomes measured were mortality, induced exophily (exit rate), blood feeding inhibition and deterrence (entry rate). Data were analysed using linear mixed effect regression and Bland-Altman comparison of paired differences. RESULTS: A total of 613 mosquitoes were collected in 36 nights, of which 13.5% were Anopheles gambiae sensu lato, 21% Anopheles funestus sensu stricto, 38% Mansonia species and 28% Culex species. Ifakara huts caught three times more mosquitoes than the East African and West African huts, while the West African huts caught significantly fewer mosquitoes than the other hut types. Mosquito densities were low, very little mosquito exit was measured in any of the huts with no measurable exophily caused by the use of either Olyset or Permanet. When the huts were directly compared, the West African huts measured greater exophily than other huts. As unholed nets were used in the experiments and few mosquitoes were captured, it was not possible to measure difference in feeding success either between treatments or hut types. In each of the hut types there was increased mortality when Permanet or Olyset were present inside the huts compared to the control, however this did not vary between the hut types. CONCLUSIONS: Both East African and Ifakara huts performed in a similar way although Ifakara huts allowed more mosquitoes to enter, increasing data power. The work convincingly demonstrates that the East African huts and Ifakara huts collect substantially more mosquitoes than the West African huts

Deletions of the Plasmodium falciparum histidine-rich protein 2/3 genes are common in field isolates from north-eastern Tanzania.

Plasmodium falciparum parasites lacking histidine-rich protein 2 and 3 (pfhrp2/3) genes have been reported in several parts of the world. These deletions are known to compromise the effectiveness of HRP2-based malaria rapid diagnostic tests (HRP2-RDT). The National Malaria Control Programme (NMCP) in Tanzania adopted HRP2-RDTs as a routine tool for malaria diagnosis in 2009 replacing microscopy in many Health facilities. We investigated pfhrp2/3 deletions in 122 samples from two areas with diverse malaria transmission intensities in Northeastern Tanzania. Pfhrp2 deletion was confirmed in 1.6% of samples while pfhrp3 deletion was confirmed in 50% of samples. We did not find parasites with both pfhrp2 and pfhrp3 deletions among our samples. Results from this study highlight the need for systematic surveillance of pfhrp2/3 deletions in Tanzania to understand their prevalence and determine their impact on the performance of mRDT

How have ART treatment programmes changed the patterns of excess mortality in people living with HIV? Estimates from four countries in East and Southern Africa

Background: Substantial falls in the mortality of people living with HIV (PLWH) have been observed since the introduction of antiretroviral therapy (ART) in sub-Saharan Africa. However, access and uptake of ART have been variable in many countries. We report the excess deaths observed in PLWH before and after the introduction of ART. We use data from five longitudinal studies in Malawi, South Africa, Tanzania, and Uganda, members of the network for Analysing Longitudinal Population-based HIV/AIDS data on Africa (ALPHA). Methods: Individual data from five demographic surveillance sites that conduct HIV testing were used to estimate mortality attributable to HIV, calculated as the difference between the mortality rates in PLWH and HIV-negative people. Excess deaths in PLWH were standardized for age and sex differences and summarized over periods before and after ART became generally available. An exponential regression model was used to explore differences in the impact of ART over the different sites. Results: 127,585 adults across the five sites contributed a total of 487,242 person years. Before the introduction of ART, HIV-attributable mortality ranged from 45 to 88 deaths per 1,000 person years. Following ART availability, this reduced to 14–46 deaths per 1,000 person years. Exponential regression modeling showed a reduction of more than 50% (HR =0.43, 95% CI: 0.32–0.58), compared to the period before ART was available, in mortality at ages 15–54 across all five sites. Discussion: Excess mortality in adults living with HIV has reduced by over 50% in five communities in sub-Saharan Africa since the advent of ART. However, mortality rates in adults living with HIV are still 10 times higher than in HIV-negative people, indicating that substantial improvements can be made to reduce mortality further. This analysis shows differences in the impact across the sites, and contrasts with developed countries where mortality among PLWH on ART can be similar to that of the general population. Further research is urgently needed to establish why the different impacts on mortality were observed and how the care and treatment programmes in these countries can be more effective in reducing mortality further

Ethnobotanical study of some of mosquito repellent plants in north-eastern Tanzania

The use of plant repellents against nuisance biting insects is common and its potential for malaria vector control requires evaluation in areas with different level of malaria endemicity. The essential oils of Ocimum suave and Ocimum kilimandscharicum were evaluated against malaria vectors in north-eastern Tanzania. An ethnobotanical study was conducted at Moshi in Kilimanjaro region north-eastern Tanzania, through interviews, to investigate the range of species of plants used as insect repellents. Also, bioassays were used to evaluate the protective potential of selected plants extracts against mosquitoes. The plant species mostly used as repellent at night are: fresh or smoke of the leaves of O. suave and O. kilimandscharicum (Lamiaceae), Azadirachta indica (Meliaceae), Eucalyptus globules (Myrtaceae) and Lantana camara (Verbenaceae). The most popular repellents were O. kilimandscharicum (OK) and O. suave (OS) used by 67% out of 120 households interviewed. Bioassay of essential oils of the two Ocimum plants was compared with citronella and DEET to study the repellence and feeding inhibition of untreated and treated arms of volunteers. Using filter papers impregnated with Ocimum extracts, knockdown effects and mortality was investigated on malaria mosquito Anopheles arabiensis and Anopheles gambiae, including a nuisance mosquito, Culex quinquefasciatus. High biting protection (83% to 91%) and feeding inhibition (71.2% to 92.5%) was observed against three species of mosquitoes. Likewise the extracts of Ocimum plants induced KD90 of longer time in mosquitoes than citronella, a standard botanical repellent. Mortality induced by standard dosage of 30 mg/m2 on filter papers, scored after 24 hours was 47.3% for OK and 57% for OS, compared with 67.7% for citronella. The use of whole plants and their products as insect repellents is common among village communities of north-eastern Tanzania and the results indicate that the use of O. suave and O. kilimandscharicum as a repellent would be beneficial in reducing vector biting. The widespread use of this approach has a potential to complement other control measures

Inhibition of arginase ameliorates experimental ulcerative colitis in mice

Nitric oxide (NO) is produced from the conversion of L-arginine by NO synthase (NOS) and regulates a variety of processes in the gastrointestinal tract. Considering the increased activity of arginase in colitis tissue, it is speculated that arginase could inhibit NO synthesis by competing for the same L-arginine substrate, resulting in the exacerbation of colitis. We examined the role of arginase and its relationship to NO metabolism in dextran sulfate sodium (DSS)-induced colitis. Experimental colitis was induced in mice by administration of 2.5% DSS in drinking water for 8 days. Treatment for arginase inhibition was done by once daily intraperitoneal injection of N-omega-hydroxy-norarginine (nor-NOHA). On day 8, we evaluated clinical parameters (body weight, disease activity index, and colon length), histological features, the activity and expression of arginase, L-arginine content, the expression of NO synthase (NOS), and the concentration of NO end-product (NOx: nitrite + nitrate). Administration of nor-NOHA improved the worsened clinical parameters and histological features in DSS-induced colitis. Treatment with nor-NOHA attenuated the increased activity of arginase, upregulation of arginase. at both mRNA and protein levels, and decreased the content of L-arginine in colonic tissue in the DSS-treated mice. Conversely, despite the decreased expression of NOS2 mRNA, the decreased concentration of NOx in colonic tissues was restored to almost normal levels. The consumption of L-arginine by arginase could lead to decreased production of NO from NOS, contributing to the pathogenesis of the colonic inflammation; thus, arginase inhibition might be effective for improving colitis

Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

Background: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions. Methods: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering. Results: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48 (95% CI 1.63–3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19–1.74), p < 0.001); history of transfusion (1.48(1.13–1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21–1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features), who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47–0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47–0.76), p < 0.001); younger-age (1.07 (1.03–1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46–0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23–2.44) and 1.46(1.18–1.82) respectively compared to no splenomegaly. Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe malaria. Conclusions: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important. Trial registration: ISRCTN ISRCTN84086586. Keywords: Severe anaemia, Readmissio

Comparative efficacies of permethrin-, deltamethrin- and alpha-cypermethrin-treated nets, against Anopheles arabiensis and Culex quinquefasciatus in northern Tanzania.

Mosquito nets treated with permethrin, deltamethrin or alpha-cypermethrin at 25 mg/m(2) were evaluated in experimental huts in an area of rice irrigation near Moshi, in northern Tanzania. The nets were deliberately holed to resemble worn nets. The nets treated with permethrin offered the highest personal protection against Anopheles arabiensis (61.6% reduction in fed mosquitoes) and Culex quinquefasciatus (25.0%). Deltamethrin and alpha-cypermethrin provided lower personal protection against An. arabiensis (46.4% and 45.6%, respectively) and no such protection against Cx. quinquefasciatus. Permethrin performed poorly in terms of mosquito mortality, however, killing only 15.2% of the An. arabiensis and 9.2% of the Cx. quinquefasciatus exposed to the nets treated with this pyrethroid (after correcting for control mortality). The alpha-cypermethrin and deltamethrin performed marginally better, with respective mortalities of 32.8% and 33.0% for An. arabiensis and 19.4% and 18.9% for Cx quinquefasciatus. The poor killing effect of permethrin was confirmed in a second trial where a commercial, long-lasting insecticidal net based on this pyrethroid (Olyset) produced low mortalities in both An. arabiensis (11.8%) and Cx. quinquefasciatus (3.6%). Anopheles arabiensis survivors collected from the verandahs of the experimental huts and tested on 0.75%-permethrin and 0.05%-deltamethrin papers, in World Health Organization susceptibility kits, showed mortalities of 96% and 100%, respectively. The continued use of permethrin-treated nets is recommended for personal protection against An. arabiensis. In control programmes that aim to interrupt transmission of pathogens by mosquitoes and/or manage pyrethroid resistance in such vectors, a combination of a pyrethroid and another insecticide with greater killing effect should be considered

Ternary critical point determination of experimental demixion curve: calculation method, relevance and limits

In many cases of miscibility gap in ternary systems, one critical point at least, stable or metastable, can be observed under isobaric and isothermal conditions. The experimental determination of this invariant point is difficult but its knowledge is essential. The authors propose a method for calculating the composition of the invariant solution starting from the composition of the liquid phases in equilibrium. The computing method is based on the barycentric properties of the conjugate solutions (binodal points) and an extension of the straight diameter method. A systematic study was carried out on a large number of ternary systems involving diverse constituents (230 sets ternary systems at various temperatures). Thus the results are presented and analyzed by means of consistency tests