Policy environment and male circumcision for HIV prevention: Findings from a situation analysis study in Tanzania

<p>Abstract</p> <p>Background</p> <p>Male circumcision (MC) has been shown to be effective against heterosexual acquisition of HIV infection and is being scaled up as an additional strategy against HIV in several countries of Africa. However, the policy environment (whether to formulate new specific policy on MC or adapts the existing ones); and the role of various stakeholders in the MC scale up process in Tanzania was unclear. We conducted this study as part of a situation analysis to understand the attitudes of policy makers and other key community and health authority decision makers towards MC, policy and regulatory environment, and the readiness of a health system to accommodate scaling up of MC services.</p> <p>Methods</p> <p>We conducted 36 key informants' interviews with a broad range of informants including civil servants, religious leaders, cultural and traditional gatekeepers and other potential informants. Study informants were selected at the national level, regional, district and community levels to represent both traditionally circumcising and non-circumcising communities.</p> <p>Results</p> <p>Study informants had positive attitudes and strong beliefs towards MC. Key informants in traditionally non-circumcising districts were willing to take their sons for medically performed MC. Religious leaders and traditional gatekeepers supported MC as it has been enshrined in their holy scripts and traditional customs respectively. Civil servants highlighted the need for existence of enabling policy and regulatory environment in the form of laws, regulations and guidelines that will ensure voluntary accessibility, acceptability, quality and safety for those in need of MC services. Majority of informants urged the government to make improvements in the health system at all levels to ensure availability of adequate trained personnel, infrastructure, equipment, and supplies for MC scale up, and insisted on the involvement of different MC stakeholders as key components in effective roll out of medically performed MC programme in the country.</p> <p>Conclusions</p> <p>Findings from the situation analysis in Tanzania have shown that despite the absence of a specific policy on MC, basic elements of enabling policy environment at national, regional, district and community levels are in place for the implementation of MC scale up programme.</p

The costs of accessible quality assured syphilis diagnostics: informing quality systems for rapid syphilis tests in a Tanzanian setting.

OBJECTIVES: To determine the costs of Rapid Syphilis Test (RSTs) as compared with rapid plasma reagin (RPR) when implemented in a Tanzanian setting, and to determine the relative impact of a quality assurance (QA) system on the cost of RST implementation. METHODS: The incremental costs for RPR and RST screening programmes in existing antenatal care settings in Geita District, Tanzania were collected for 9 months in subsequent years from nine health facilities that varied in size, remoteness and scope of antenatal services. The costs per woman tested and treated were estimated for each facility. A sensitivity analysis was constructed to determine the impact of parameter and model uncertainty. FINDINGS: In surveyed facilities, a total of 6362 women were tested with RSTs compared with 224 tested with RPR. The range of unit costs was $1.76-$3.13 per woman screened and $12.88-$32.67 per woman treated. Unit costs for the QA system came to $0.51 per woman tested, of which 50% were attributed to salaries and transport for project personnel. CONCLUSIONS: Our results suggest that rapid syphilis diagnostics are very inexpensive in this setting and can overcome some critical barriers to ensuring universal access to syphilis testing and treatment. The additional costs for implementation of a quality system were found to be relatively small, and could be reduced through alterations to the programme design. Given the potential for a quality system to improve quality of diagnosis and care, we recommend that QA activities be incorporated into RST roll-out

Risk factors for malaria infection prevalence and household vector density between mass distribution campaigns of long-lasting insecticidal nets in North-western Tanzania.

BACKGROUND: Long-lasting insecticidal nets (LLINs) are the most widely deployed vector control intervention in sub-Saharan Africa to prevent malaria. Recent reports indicate selection of pyrethroid insecticide resistance is widespread in mosquito vectors. This paper explores risk factors associated with malaria infection prevalence and vector density between mass distribution campaigns, changes in net coverage, and loss of protection in an area of high pyrethroid resistance in Northwest Tanzania. METHODS: A cross sectional malaria survey of 3456 children was undertaken in 2014 in Muleba district, Kagera region west of Lake Victoria. Vector density was assessed using indoor light traps and outdoor tent traps. Anophelines were identified to species using PCR and tested for Plasmodium falciparum circumsporozoite protein. Logistic regression was used to identify household and environmental factors associated with malaria infection and regression binomial negative for vector density. RESULTS: LLIN use was 27.7%. Only 16.9% of households had sufficient nets to cover all sleeping places. Malaria infection was independently associated with access to LLINs (OR: 0.57; 95% CI 0.34-0.98). LLINs less than 2 years old were slightly more protective than older LLINs (53 vs 65% prevalence of infection); however, there was no evidence that LLINs in good condition (hole index < 65) were more protective than LLINs, which were more holed. Other risk factors for malaria infection were age, group, altitude and house construction quality. Independent risk factors for vector density were consistent with malaria outcomes and included altitude, wind, livestock, house quality, open eaves and LLIN usage. Indoor collections comprised 4.6% Anopheles funestus and 95.4% Anopheles gambiae of which 4.5% were Anopheles arabiensis and 93.5% were Anopheles gambiae sensu stricto. CONCLUSION: Three years after the mass distribution campaign and despite top-ups, LLIN usage had declined considerably. While children living in households with access to LLINs were at lower risk of malaria, infection prevalence remained high even among users of LLINs in good condition. While effort should be made to maintain high coverage between campaigns, distribution of standard pyrethroid-only LLINs appears insufficient to prevent malaria transmission in this area of intense pyrethroid resistance

Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial.

BACKGROUND: Progress in malaria control is under threat by wide-scale insecticide resistance in malaria vectors. Two recent vector control products have been developed: a long-lasting insecticidal net that incorporates a synergist piperonyl butoxide (PBO) and a long-lasting indoor residual spraying formulation of the insecticide pirimiphos-methyl. We evaluated the effectiveness of PBO long-lasting insecticidal nets versus standard long-lasting insecticidal nets as single interventions and in combination with the indoor residual spraying of pirimiphos-methyl. METHODS: We did a four-group cluster randomised controlled trial using a two-by-two factorial design of 48 clusters derived from 40 villages in Muleba (Kagera, Tanzania). We randomly assigned these clusters using restricted randomisation to four groups: standard long-lasting insecticidal nets, PBO long-lasting insecticidal nets, standard long-lasting insecticidal nets plus indoor residual spraying, or PBO long-lasting insecticidal nets plus indoor residual spraying. Both standard and PBO nets were distributed in 2015. Indoor residual spraying was applied only once in 2015. We masked the inhabitants of each cluster to the type of nets received, as well as field staff who took blood samples. Neither the investigators nor the participants were masked to indoor residual spraying. The primary outcome was the prevalence of malaria infection in children aged 6 months to 14 years assessed by cross-sectional surveys at 4, 9, 16, and 21 months after intervention. The endpoint for assessment of indoor residual spraying was 9 months and PBO long-lasting insecticidal nets was 21 months. This trial is registered with ClinicalTrials.gov, number NCT02288637. FINDINGS: 7184 (68·0%) of 10 560 households were selected for post-intervention survey, and 15 469 (89·0%) of 17 377 eligible children from the four surveys were included in the intention-to-treat analysis. Of the 878 households visited in the two indoor residual spraying groups, 827 (94%) had been sprayed. Reported use of long-lasting insecticidal nets, across all groups, was 15 341 (77·3%) of 19 852 residents after 1 year, decreasing to 12 503 (59·2%) of 21 105 in the second year. Malaria infection prevalence after 9 months was lower in the two groups that received PBO long-lasting insecticidal nets than in the two groups that received standard long-lasting insecticidal nets (531 [29%] of 1852 children vs 767 [42%] of 1809; odds ratio [OR] 0·37, 95% CI 0·21-0·65; p=0·0011). At the same timepoint, malaria prevalence in the two groups that received indoor residual spraying was lower than in groups that did not receive indoor residual spraying (508 [28%] of 1846 children vs 790 [44%] of 1815; OR 0·33, 95% CI 0·19-0·55; p<0·0001) and there was evidence of an interaction between PBO long-lasting insecticidal nets and indoor residual spraying (OR 2·43, 95% CI 1·19-4·97; p=0·0158), indicating redundancy when combined. The PBO long-lasting insecticidal net effect was sustained after 21 months with a lower malaria prevalence than the standard long-lasting insecticidal net (865 [45%] of 1930 children vs 1255 [62%] of 2034; OR 0·40, 0·20-0·81; p=0·0122). INTERPRETATION: The PBO long-lasting insecticidal net and non-pyrethroid indoor residual spraying interventions showed improved control of malaria transmission compared with standard long-lasting insecticidal nets where pyrethroid resistance is prevalent and either intervention could be deployed to good effect. As a result, WHO has since recommended to increase coverage of PBO long-lasting insecticidal nets. Combining indoor residual spraying with pirimiphos-methyl and PBO long-lasting insecticidal nets provided no additional benefit compared with PBO long-lasting insecticidal nets alone or standard long-lasting insecticidal nets plus indoor residual spraying. FUNDING: UK Department for International Development, Medical Research Council, and Wellcome Trust

The independent effect of living in malaria hotspots on future malaria infection: an observational study from Misungwi, Tanzania.

BACKGROUND: As malaria transmission declines, continued improvements of prevention and control interventions will increasingly rely on accurate knowledge of risk factors and an ability to define high-risk areas and populations at risk for focal targeting of interventions. This paper explores the independent association between living in a hotspot and prospective risk of malaria infection. METHODS: Malaria infection status defined by nPCR and AMA-1 status in year 1 were used to define geographic hotspots using two geospatial statistical methods (SaTScan and Kernel density smoothing). Other malaria risk factors for malaria infection were explored by fitting a multivariable model. RESULTS: This study demonstrated that residing in infection hotspot of malaria transmission is an independent predictor of malaria infection in the future. CONCLUSION: It is likely that targeting such hotspots with better coverage and improved malaria control strategies will result in more cost-efficient uses of resources to move towards malaria elimination

Cost Implications of Improving Malaria Diagnosis: Findings from North-Eastern Tanzania

BACKGROUND: Over diagnosis of malaria contributes to improper treatment, wastage of drugs and resistance to the few available drugs. This paper attempts to estimate the rates of over diagnosis of malaria among children attending dispensaries in rural Tanzania and examines the potential cost implications of improving the quality of diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: The magnitude of over diagnosis of malaria was estimated by comparing the proportion of outpatient attendees of all ages clinically diagnosed as malaria to the proportion of attendees having a positive malaria rapid diagnostic test over a two month period. Pattern of causes of illness observed in a or=5 year age group in the lower transmission site (RR 14.0 95%CI 8.2-24.2). In the low transmission site the proportion of morbidity attributable to malaria was substantially lower in <2 year old cohort compared to children seen at routine care system. (0.08% vs 28.2%; p<0.001). A higher proportion of children were diagnosed with ARI in the <2 year old cohort compared to children seen at the routine care system ( 42% vs 26%; p<0.001). Using a RDT reduced overall drug and diagnostic costs by 10% in the high transmission site and by 15% in the low transmission site compared to total diagnostic and drug costs of treatment based on clinical judgment in routine health care system. IMPLICATIONS: The introduction of RDTs is likely to lead to financial savings. However, improving diagnosis to one disease may lead to over diagnosis of another illness. Quality improvement is complex but introducing RDTs for the diagnosis of malaria is a good start

Duration of Protection Against Clinical Malaria Provided by Three Regimens of Intermittent Preventive Treatment in Tanzanian Infants

BACKGROUND: Intermittent preventive treatment in infants (IPTi) is a new malaria control tool. However, it is uncertain whether IPTi works mainly through chemoprophylaxis or treatment of existing infections. Understanding the mechanism is essential for development of replacements for sulfadoxine-pyrimethamine (SP) where it is no longer effective. This study investigated how protection against malaria given by SP, chlorproguanil-dapsone (CD) and mefloquine (MQ), varied with time since administration of IPTi. METHODS AND FINDINGS: A secondary analysis of data from a randomised, placebo-controlled trial in an area of high antifolate resistance in Tanzania was conducted. IPTi using SP, CD, MQ or placebo was given to 1280 infants at 2, 3 and 9 months of age. Poisson regression with random effects to adjust for potential clustering of malaria episodes within children was used to calculate incidence rate ratios for clinical malaria in defined time strata following IPTi. The short-acting antimalarial CD gave no protection against clinical malaria, whereas long-acting MQ gave two months of substantial protection (protective efficacy (PE) 73.1% (95% CI: 23.9, 90.5) and 73.3% (95% CI: 0, 92.9) in the first and second month respectively). SP gave some protection in the first month after treatment (PE 64.5% (95% CI: 10.6, 85.9)) although it did not reduce the incidence of malaria up to 12 months of age. There was no evidence of either long-term protection or increased risk of malaria for any of the regimens. CONCLUSION: Post-treatment chemoprophylaxis appears to be the main mechanism by which IPTi protects children against malaria. Long-acting antimalarials are therefore likely to be the most effective drugs for IPTi, but as monotherapies could be vulnerable to development of drug resistance. Due to concerns about tolerability, the mefloquine formulation used in this study is not suitable for IPTi. Further investigation of combinations of long-acting antimalarials for IPTi is needed. TRIAL REGISTRATION: Clinicaltrials.gov NCT00158574

Will a lack of fabric durability be their downfall? Impact of textile durability on the efficacy of three types of dual-active-ingredient long-lasting insecticidal nets: a secondary analysis on malaria prevalence and incidence from a cluster-randomized trial in north-west Tanzania.

BACKGROUND: The Dual-Active Ingredient long-lasting insecticidal nets (Dual-AI LLIN) have been developed to counteract the reduced efficacy of pyrethroid (PY)-only nets due to widespread pyrethroid insecticide resistance in malaria vector mosquitoes. They constitute half of the nets distributed in sub-Saharan Africa between 2022 and 2024. However, their effectiveness once they develop holes is unclear, particularly in pyrethroid-resistant settings. This study evaluates the textile integrity of three dual- AI LLINs compared to standard PY LLN, over 3 years of use in a community in Tanzania and the associated impact on malaria prevalence and incidence. METHODS: A secondary analysis of data from a randomized controlled trial (RCT) in North-western Tanzania was conducted to evaluate the effectiveness of α-cypermethrin only; pyriproxyfen and α-cypermethrin (PPF-PY); chlorfenapyr and α-cypermethrin (chlorfenapyr-PY); and the synergist piperonyl butoxide and permethrin (PBO-PY) LLINs on malaria infection prevalence and case incidence. The association between the net textile condition and 1/malaria prevalence over 3 years of use between 2019 and 2022, and 2/malaria case incidence in a cohort of children over 2 years of follow-up was assessed between 2019 and 2021. RESULTS: There was no significant association between damaged (OR 0.98, 95% CI 0.71-1.37, p-value  = 0.655) and too-torn (OR 1.07, 95% CI 0.77-1.47, p-value = 0.694) compared to intact nets on malaria prevalence for all net types. However, there were reduced rates of malaria case incidence in children sleeping under a net in good condition compared to too-torn nets (incidence rate ratio (IRR) 0.76 [95% CI 0.63-0.92], p = 0.005). Malaria incidence was also consistently lower in too-torn PBO-PY LLIN (IRR = 0.37 [95% CI 0.19-0.72], p = 0.003) and chlorfenapyr-PY LLIN (IRR = 0.45 [95% CI 0.33-0.97], p = 0.053) compared to an intact PY-only LLIN during the first year of follow up. In year 2, the incidence was only significantly lower in intact chlorfenapyr-PY LLIN (IRR = 0.49 [95% CI 0.29-0.81], p = 0.006) compared to intact PY LLIN. CONCLUSION: The study confirmed that sleeping under a chlorfenapyr-PY LLIN or PBO-PY LLIN offered superior protection to pyrethroid-only nets even when torn. Preventing the development of holes is essential as they impact the level of protection offered against malaria infection. TRIAL REGISTRATION: ClinicalTrials.gov, number (NCT03554616)

Personal protection with PBO-pyrethroid synergist-treated nets after 2 years of household use against pyrethroid-resistant Anopheles in Tanzania.

BACKGROUND: The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use. METHODS: From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays. RESULTS: Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 0.03, 95% CI 0.01-0.13, p < 0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories, but more were collected inside the more damaged nets (HI ≥ 643) than in less damaged (HI 0-64) nets (DR: 6.4, 95% CI 1.1-36.0, p = 0.037). In bioassay, mortality of An. gambiae s.l. was higher with Olyset Plus than with Olyset nets for new nets (76.8% vs 27.5%) and nets used for 20 months (56.8% vs 12.8%); similar trends were observed with An. funestus. CONCLUSION: The PBO-Py LLINs provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid-resistant An. gambiae sensu stricto (s.s.) and An. funestus collected from inside Olyset Plus nets, irrespective of HI category, as compared to Olyset nets

Risks of Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficient Infants Exposed to Chlorproguanil-Dapsone, Mefloquine and Sulfadoxine-Pyrimethamine as Part of Intermittent Presumptive Treatment of Malaria in Infants.

BACKGROUND: Chlorproguanil-dapsone (CD) has been linked to hemolysis in symptomatic glucose-6-phosphate dehydrogenase deficient (G6PDd) children. Few studies have explored the effects of G6PD status on hemolysis in children treated with Intermittent Preventive Treatment in infants (IPTi) antimalarial regimens. We sought to examine the joint effects of G6PD status and IPTi antimalarial treatment on incidence of hemolysis in asymptomatic children treated with CD, sulfadoxine-pyrimethamine (SP), and mefloquine (MQ). METHODS: A secondary analysis of data from a double-blind, placebo-controlled trial of IPTi was conducted. Hemoglobin (Hb) measurements were made at IPTi doses, regular follow-up and emergency visits. G6PD genotype was determined at 9 months looking for SNPs for the A- genotype at coding position 202. Multivariable linear and logistic regression models were used to examine hemolysis among children with valid G6PD genotyping results. Hemolysis was defined as the absolute change in Hb or as any post-dose Hb <8 g/dL. These outcomes were assessed using either a single follow-up Hb on day 7 after an IPTi dose or Hb obtained 1 to 14 or 28 days after each IPTi dose. FINDINGS: Relative to placebo, CD reduced Hb by approximately 0.5 g/dL at day 7 and within 14 days of an IPTi dose, and by 0.2 g/dL within 28 days. Adjusted declines in the CD group were larger than in the MQ and SP groups. At day 7, homo-/hemizygous genotype was associated with higher odds of Hb <8 g/dL (adjusted odds ratio = 6.7, 95% CI 1.7 to 27.0) and greater absolute reductions in Hb (-0.6 g/dL, 95% CI -1.1 to 0.003). There was no evidence to suggest increased reductions in Hb among homo-/hemizygous children treated with CD compared to placebo, SP or MQ. CONCLUSIONS: While treatment with CD demonstrated greater reductions in Hb at 7 and 14 days after an IPTi dose compared to both SP and MQ, there was no evidence that G6PD deficiency exacerbated the adverse effects of CD, despite evidence for higher hemolysis risk among G6PDd infants