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Biomedical subjects

Hassan Mshinda

Publications and source records attributed to Hassan Mshinda.

At least 19 recordsLinked to original sources

Adaptation of the ultrasensitive HIV-1 p24 antigen assay to dried blood spot testing.

Implementation of molecular tests for the assessment of pediatric HIV-1 infection in resource-limited countries is difficult because of technical complexity and costs. Alternatives like the ultrasensitive HIV-1 p24 antigen enzyme-linked immunosorbent assay have therefore been proposed. We have now adapted this test to dried blood spot (DBS) plasma p24 antigen (p24). High background activity was recognized as originating from endogenous peroxidase and eliminated by H2O2 quenching. The assay was evaluated with 72 pediatric specimens from Tanzania and with 210 pediatric or adult specimens from Switzerland. A real-time polymerase chain reaction assay for DBS DNA and/or plasma RNA identified HIV-1 infection in 38 Tanzanian children. HIV-1 subtypes included 18 C, 9 A1, 8 D, 1 AC, 1 J-like, and 1 unidentified. The detection rates for the different assays were as follows: DBS-p24, 32 (84%) of 38 samples; DBS DNA, 30 (79%) of 38 samples; plasma-p24, 23 (85%) of 27 samples; and plasma RNA, 30 (100%) of 30 samples. False-negative DBS-p24 was associated with subtype D (P < 0.01). DBS-p24 detection for non-D subtypes was 93% (95% confidence interval: 81% to 99%), and for subtype C, it was 94% (95% confidence interval: 76% to 99%). Specificity among 193 HIV-negative DBS samples was 100%. Correlation of DBS-p24 and plasma-p24 concentrations was excellent (R = 0.83, P < 0.0001). DBS-p24 is thus a promising alternative to molecular tests for HIV-1 in subtype C regions. It should now be evaluated in large studies of children for accurate assessment of diagnostic sensitivity.

Adolescent↗

Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania.

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance.

Animals↗

Risk factors for surgical site infection in a Tanzanian district hospital: a challenge for the traditional National Nosocomial Infections Surveillance system index.

The incidence of surgical site infections (SSIs) was 24% in a district hospital in Tanzania. Wound classification was not an independent risk factor for SSI, indicating that risk scores developed in industrialized countries may require adjustments for nonindustrialized countries. The National Nosocomial Infections Surveillance system score required adjustments to reliably predict SSI, probably to account for improper hygiene and the lack of adjustment for the duration of surgery (defined as the 75th percentile of the duration for each type of operative procedure) to reflect local circumstances. Multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus and gram-negative pathogens expressing broad-spectrum beta-lactamases, have already emerged.

Adult↗

Decreased availability of antimalarials in the private sector following the policy change from chloroquine to sulphadoxine-pyrimethamine in the Kilombero Valley, Tanzania.

BACKGROUND: Malaria control strategies emphasize the need for prompt and effective treatment of malaria episodes. To increase treatment efficacy, Tanzania changed its first-line treatment from chloroquine to sulphadoxine-pyrimethamine (SP) in 2001. The effect of this policy change on the availability of antimalarials was studied in rural south-eastern Tanzania. METHODS: In 2001 and 2004, the study area was searched for commercial outlets selling drugs and their stocks were recorded. Household information was obtained from the local Demographic Surveillance System. RESULTS: From 2001 to 2004, the number of general shops stocking drugs increased by 15% and the number of drug stores nearly doubled. However, the proportion of general shops stocking antimalarials dropped markedly, resulting in an almost 50% decrease of antimalarial selling outlets. This led to more households being located farther from a treatment source. In 2004, five out of 25 studied villages with a total population of 13,506 (18%) had neither a health facility, nor a shop as source of malaria treatment. CONCLUSION: While the change to SP resulted in a higher treatment efficacy, it also led to a decreased antimalarial availability in the study area. Although there was no apparent impact on overall antimalarial use, the decline in access may have disproportionately affected the poorest and most remote groups. In view of the imminent policy change to artemisinin-based combination therapy these issues need to be addressed urgently if the benefits of this new class of antimalarials are to be extended to the whole population.

Analgesics, Non-Narcotic↗

Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania.

BACKGROUND: Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. METHODS: The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracted by Chelex method from blood samples collected and preserved on filter papers. Subsequently, polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP) were applied to detect the SP resistance-associated point mutations on dhfr and dhps. Commonly reported point mutations at codons 51, 59, 108 and 164 in the dhfr and codons 437, 540 and 581 in the dhps domains were examined. RESULTS: Children infected with parasites harbouring a range of single to quintuple dhfr/dhps mutations were erratically cured with SP. However, the quintuple dhfr/dhps mutant genotypes were mostly associated with treatment failures. High proportion of SP resistance-associated point mutations was detected in this study but the adequate clinical response (89.4%) observed clinically at day 14 of follow up reflects the role of semi-immunity protection and parasite clearance in the population. CONCLUSION: In monitoring drug resistance to SP, concurrent studies on possible confounding factors pertaining to development of resistance in falciparum malaria should be considered. The SP resistance potential detected in this study, cautions on its useful therapeutic life as an interim first-line drug against malaria in Tanzania and other malaria-endemic countries.

Animals↗

Ecologists can enable communities to implement malaria vector control in Africa.

BACKGROUND: Integrated vector management (IVM) for malaria control requires ecological skills that are very scarce and rarely applied in Africa today. Partnerships between communities and academic ecologists can address this capacity deficit, modernize the evidence base for such approaches and enable future scale up. METHODS: Community-based IVM programmes were initiated in two contrasting settings. On Rusinga Island, Western Kenya, community outreach to a marginalized rural community was achieved by University of Nairobi through a community-based organization. In Dar es Salaam, Tanzania, Ilala Municipality established an IVM programme at grassroots level, which was subsequently upgraded and expanded into a pilot scale Urban Malaria Control Programme with support from national academic institutes. RESULTS: Both programmes now access relevant expertise, funding and policy makers while the academic partners benefit from direct experience of community-based implementation and operational research opportunities. The communities now access up-to-date malaria-related knowledge and skills for translation into local action. Similarly, the academic partners have acquired better understanding of community needs and how to address them. CONCLUSION: Until sufficient evidence is provided, community-based IVM remains an operational research activity. Researchers can never directly support every community in Africa so community-based IVM strategies and tactics will need to be incorporated into undergraduate teaching programmes to generate sufficient numbers of practitioners for national scale programmes. Academic ecologists at African institutions are uniquely positioned to enable the application of practical environmental and entomological skills for malaria control by communities at grassroots level and should be supported to fulfil this neglected role.

Africa↗

Moving up from 3 by 5.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Molecular genotyping to distinguish between recrudescents and new infections in treatment trials of Plasmodium falciparum malaria conducted in Sub-Saharan Africa: adjustment of parasitological outcomes and assessment of genotyping effectiveness.

Molecular genotyping of baseline and post-treatment recurrent Plasmodium falciparum is recommended to distinguish recrudescent from new infections. However, genotyping performance and adjustment of treatment outcomes have not been evaluated in large field trials. Parasitological outcomes were assessed in nine double-blinded trials of uncomplicated P. falciparum malaria in African children treated with artesunate/placebo plus standard monotherapies. Day 28 failure rates were adjusted by stepwise genotyping the P. falciparum glutamate rich protein (glurp), merozoite surface protein 1 (msp1) and 2 (msp2). We calculated overall and laboratory genotyping performance and compared unadjusted (crude) and PCR-adjusted outcomes. 3455 (93.6%) of 3691 enrolled patients were evaluable by Day 28. 767 (22%) had post-Day 14 recurrent parasitemias of which 686 could be genotyped: 246 were recrudescences, 286 new infections and 154 unresolved. The overall and laboratory genotyping performance were 69 (12-100)% and 78 (50-100)%, respectively. The mean Day 28 crude parasitological failure rate was 44 (range 3-87)%. PCR-adjusted rates were 36 (range 2-86)% if unresolved infections were counted as failures or 33 (range 2-86)% if excluded from analysis. The overall difference between crude Day 28 and Day 14 failure rates was 22% (95% CI 20.3, 24.6) but decreased to 14% (95% CI 12.1, 16.3) if unresolved infections are counted as failures, or to 11% (95% CI 9.8, 16.3) if unresolved infections are excluded from the analysis. Genotyping refined treatment outcomes but diligence is needed in sample collection and analysis to improve its performance. Our findings support the WHO recommendation of PCR genotyping in malaria clinical trials and suggest that stepwise genotyping of only two loci (msp2 and msp1 or glurp) can reliably discriminate recrudescences from new infections.

Africa South of the Sahara↗

Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies.

BACKGROUND: Systematic surveillance for resistant malaria shows high level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP) across eastern and southern parts of Africa. This study assessed in vivo SP efficacy after two years of use as an interim first-line drug in Tanzania, and determined the rates of treatment failures obtained after 14 and 28 days of follow-up. METHODS: The study was conducted in the Ipinda, Mlimba and Mkuranga health facilities in Tanzania. Children aged 6-59 months presenting with raised temperature associated exclusively with P. falciparum (1,000-100,000 parasites per microl) were treated with standard dose of SP. Treatment responses were classified according to the World Health Organization (WHO) definition as Adequate Clinical and Parasitological Response (ACPR), Early Treatment Failure (ETF), Late Clinical Failure (LCF) and Late Parasitological Failure (LPF) on day 14 and day 28. RESULTS: Overall 196 (85.2%) of 230 patients had ACPR on day 14 but only 116 (50.9%) on day 28 (57.7% after excluding new infections by parasite genotyping). Altogether 21 (9.1%) and 13 (5.7%) of the 230 patients assessed up to day 14 and 39 (17.1%) and 55 (24.1%) of the 228 followed up to day 28 had clinical and parasitological failure, respectively. CONCLUSION: These findings indicate that SP has low therapeutic value in Tanzania. The recommendation of changing first line treatment to artemether + lumefantrine combination therapy from early next year is, therefore, highly justified. These findings further stress that, for long half-life drugs such as SP, establishment of cut-off points for policy change in high transmission areas should consider both clinical and parasitological responses beyond day 14.

Animals↗

Impact of Integrated Management of Childhood Illness on inequalities in child health in rural Tanzania.

We examined the impact of the Integrated Management of Childhood Illness (IMCI) strategy on the equality of health outcomes and access across socioeconomic gradients in rural Tanzania, by comparing changes in inequities between 1999 and 2002 in two districts with IMCI (Morogoro Rural and Rufiji) and two without (Kilombero and Ulanga). Equity differentials for six child health indicators (underweight, stunting, measles immunization, access to treated and untreated nets, treatment of fever with antimalarial) improved significantly in IMCI districts compared with comparison districts (p<0.05), while four indicators (wasting, DPT coverage, caretakers' knowledge of danger signs and appropriate careseeking) improved significantly in comparison districts compared with IMCI districts (p<0.05). The largest improvements were observed for stunting among children between 24-59 months of age. The concentration index improved from -0.102 in 1999 to -0.032 in 2002 for IMCI, while it remained almost unchanged -0.122 to -0.133 in comparison districts. IMCI was associated with improved equity for measles vaccine coverage, whereas the opposite was observed for DPT antigens. This study has shown how equity assessments can be incorporated in impact evaluation at relatively little additional cost, and how this may point to specific interventions that need to be reinforced. The introduction of IMCI led to improvements in child health that did not occur at the expense of equity.

Child Health Services↗

Out-of-pocket payments for under-five health care in rural southern Tanzania.

Catastrophic payments and fairness in financial contributions for health care are becoming increasing concerns for many governments. Out-of-pocket financing for health care is common in many developing countries, including Tanzania. As part of the Multi-Country Evaluation of the Integrated Management of Childhood Illness (MCE-IMCI), the objective of this paper is to explore the determinants of variation and the level of out-of-pocket payments for child health care in rural Tanzania, with and without IMCI, using data from two household surveys conducted in 1999 and 2002. We analyzed data for 833 visits to health providers for 764 children who had been sick in the 2 weeks prior to the survey and who had sought care at a 'Western' or formal health care provider. We found evidence that IMCI was associated with lower out-of-pocket costs at government facilities (Tshs.3.5 compared with Tshs.6.9 without IMCI) and in NGOs (Tshs.95.1 compared with Tshs.267.3). Out-of-pocket payments were on average Tshs.110.1 when care was sought at government primary health care facilities running a cost-sharing scheme, about 15 times higher than in those not part of the scheme (p<0.0001). Those who visited NGO facilities paid about 30 times more than those seeking care at government facilities not operating the cost-sharing scheme (p<0.0001). In conclusion, there is no doubt that health care financing mechanisms and equitable access to government facilities have a major impact on household economic burden related to under-five illness. Increasing access to IMCI-based care, however, offers an additional opportunity to reduce out-of-pocket payments, mainly through more rational use of medicines. Increasing access to IMCI-based care would not only improve inequities in financial contributions, but also in health, an important consideration for its own sake.

Child Health Services↗

Evaluation of Olyset insecticide-treated nets distributed seven years previously in Tanzania.

BACKGROUND: Insecticide-treated nets represent currently a key malaria control strategy, but low insecticide re-treatment rates remain problematic. Olyset nets are currently one of two long-lasting insecticidal nets recommended by WHO. An assessment was carried out of the effect of Olyset nets after seven years of use in rural Tanzania. METHODS: A survey of Olyset nets was conducted in two Tanzanian villages to examine their insecticide dosage, bioassay efficacy and desirability compared with ordinary polyester nets. RESULTS: Of 103 randomly selected nets distributed in 1994 to 1995, 100 could be traced. Most nets were in a condition likely to offer protection against mosquito biting. Villagers appreciated mainly the durability of Olyset trade mark nets and insecticide persistence. People disliked the small size of these nets and the light blue colour and preferred a smaller mesh size, features that can easily be modified. At equal price, 51% said they would prefer to buy an Olyset net and 49% opted for an ordinary polyester net. The average permethrin content was 33%-41% of the initial insecticide dose of 20,000 mg/Kg. Bioassay results indicated high knock-down rates at 60 minutes, but the mosquito mortality after 24 hours was rather low (mean: 34%). No significant correlation was found between bioassay results and insecticide concentration in and on the net. CONCLUSIONS: Olyset nets are popular, durable and with a much longer insecticide persistence than ordinary polyester nets. Hence, Olyset nets are one of the best choices for ITN programmes in rural malaria-endemic areas.

Animals↗

The changing epidemiology of malaria in Ifakara Town, southern Tanzania.

Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community- and hospital-based studies involving children up to the age of 5 years. There was a right shift and lowering in the age-specific parasite prevalence in the community-based cohort studies. The incidence of clinical malaria in placebo-receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital-based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria.

Age Distribution↗

Anaemia in pregnancy and infant mortality in Tanzania.

Tanzania is an area of moderate to high risk for severe anaemia during pregnancy. There is extensive literature examining the consequences of severe anaemia for pregnant women, but the impact this problem has on their infants in malaria-endemic regions is poorly understood. Between 1999 and 2001 we used a demographic surveillance system in the Kilombero Valley, Tanzania to link morbidity and socio-economic status data for 301 pregnant women to the survival of 365 days of their singleton babies, looking for evidence of an association between infant mortality and maternal haemoglobin (Hb). The hazards ratio for infant mortality amongst women who had been severely anaemic in pregnancy (Hb < 8 g/dl) was 3.1 [95% confidence interval (CI) 1.1-9.1, P = 0.04] compared with women with Hb above this level after controlling for other factors. Prevention of anaemia in pregnancy may lead to an improvement in infant survival.

Adolescent↗

Mosquito nets and the poor: can social marketing redress inequities in access?

Treated mosquito nets are a practical malaria control tool. However, implementation of efficient delivery mechanisms remains a challenge. We investigated whether social marketing of treated mosquito nets results in decreased equity in rural Tanzania, through household surveys before the start of a social marketing programme and 3 years later. About 12,000 household heads were asked about ownership of nets and other assets including a tin roof, radio, or bicycle. A socio-economic status score was developed for each household. Net ownership was calculated for households in each quintile of this score, from poorest to least poor. In 1997, about 20% of the poorest households and over 60% of the least poor households owned a mosquito net. Three years later, more than half of the poorest households owned a net, as did over 90% of the least poor: the ratio of net ownership among the poorest to least poor increased from 0.3 in 1997 to 0.6 in 2000. Social marketing in the presence of an active private sector for nets was associated with increased equity.

Animals↗

A randomized comparison of two anemia treatment regimens in Tanzanian children.

We used a prospective, open-label randomized trial to evaluate two treatment regimens in Tanzanian children two months to four years of age presenting to a hospital with a packed cell volume (PCV) < 25%. Treatment was either standard (14 days of ferrous sulfate and an antimalarial) or extended (three months of ferrous sulfate and three antimalarial treatments). The prevalence of anemia was measured two weeks after completion of treatment and six months after recruitment. Two weeks after completing treatment, the prevalence of PCV < 33% was 58% in the standard treatment arm and 44% in the extended treatment group (P = 0.04), and the mean PCV was significantly higher in the extended treatment arm (32.1%, SD = 4.5% versus 30.8%, SD = 4.9%; P = 0.031). However, there was no difference in the prevalence of PCV < 25% in the first survey, and the benefits of extended therapy were only apparent six months after recruitment in children compliant with the extended treatment (odds ratio of PCV < 25% = 0.16, P = 0.06). Compliance was satisfactory in only 39% (82 of 209) of the children in the first week of treatment. Extending the duration of therapy and improving compliance may have health benefits for anemic children in malaria-endemic settings.

Anemia, Iron-Deficiency↗