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1.  Sero-prevalence and factors associated with Toxoplasma gondii infection among pregnant women attending antenatal care in Mwanza, Tanzania 
Parasites & Vectors  2013;6:222.
Serological screening of pregnant women for Toxoplasma gondii-specific antibodies is not practiced as an antenatal care in Tanzania; and there is a limited data about sero-prevalence of T. gondii infection in developing countries. We therefore conducted this study to determine the sero-prevalence and factors associated with T. gondii infection among pregnant women attending antenatal care clinics in Mwanza, Tanzania.
Between 1st November 2012 and 31st May 2013 a total of 350 pregnant women attending antenatal care clinics in Mwanza were enrolled and screened for IgG and IgM antibodies against T. gondii using the ELISA technique.
Of 350 pregnant women, 108 (30.9%) were sero-positive for T. gondii-specific antibodies. The risk of contracting T. gondii infection increases by 7% with each yearly increase in a woman’s age (OR=1.07, 95% CI: 1.02 - 1.11, p=0.002). The sero-positivity rate of T. gondii-specific antibodies was higher among pregnant women from the urban than those from rural communities (41.5% versus 22.0%); [OR=2.2, 95% CI; 1.4 - 3.7, p=0.001]. Likewise employed/business women were more likely to get T. gondii infection than peasants (40.0% versus 25.9%) [OR=1.9, 95% CI: 1.2 - 3.0, p=0.006].
Sero-prevalence of T. gondii-specific antibodies is high among pregnant women in Mwanza with a significant proportion of women at risk of contracting primary T. gondii infections. Screening of T. gondii infections during antenatal care should be considered in Tanzania as the main strategy to minimize congenital toxoplasmosis.
PMCID: PMC3750225  PMID: 23915834
2.  Epidemiology and interactions of Human Immunodeficiency Virus – 1 and Schistosoma mansoni in sub-Saharan Africa 
Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.
PMCID: PMC3707091  PMID: 23849678
Schistosoma mansoni; HIV-1; Co-infections; Immunological interactions; Deworming
3.  Epidemiology and control of human schistosomiasis in Tanzania 
Parasites & Vectors  2012;5:274.
In Tanzania, the first cases of schistosomiasis were reported in the early 19th century. Since then, various studies have reported prevalences of up to 100% in some areas. However, for many years, there have been no sustainable control programmes and systematic data from observational and control studies are very limited in the public domain. To cover that gap, the present article reviews the epidemiology, malacology, morbidity, and the milestones the country has made in efforts to control schistosomiasis and discusses future control approaches. The available evidence indicates that, both urinary and intestinal schistosomiasis are still highly endemic in Tanzania and cause significant morbidity.Mass drug administration using praziquantel, currently used as a key intervention measure, has not been successful in decreasing prevalence of infection. There is therefore an urgent need to revise the current approach for the successful control of the disease. Clearly, these need to be integrated control measures.
PMCID: PMC3549774  PMID: 23192005
Schistosomiasis; S. mansoni; S. Mansoni; epidemiology; morbidity; control; Tanzania
4.  Association between water related factors and active trachoma in Hai district, Northern Tanzania 
Trachoma is widely distributed in sub-Saharan Africa and is mainly associated with poor water accessibility. However, these associations have never been demonstrated in some of the communities, especially in northern Tanzania. To cover that gap, the present case control study was conducted to assess the association of water related factors, general hygiene and active trachoma among preschool and school age children in Hai district, northern Tanzania.
Families reported to use > 60 litres of water per day were less likely to have active disease (OR= 0.4, 95% CI: 0.1 - 0.3; P<0.001) compared to households collecting ≤ 60 litres. The risk of having trachoma increased with increase in distance to the water point (OR= 6.5, 95% CI; 1.8 - 16.7; P= 0.003). Households members who reported to use < 2 liters of water for face washing were more likely to be trachomatous (OR= 5.12, 95% CI: 1.87-14.6, P = 0.001). Increased number of preschool children in the household was also associated with increased risk of active trachoma by 2.46 folds.
Improving water supply near the households and providing public health education focusing on improving households socio-economic status and individual hygiene especially in pre-school children in part will help to reduce the prevalence of the disease. In addition, integrating public health education with other interventions such as medical interventions remains important.
PMCID: PMC3710161  PMID: 23849896
Trachoma; Water; Hygiene; Tanzania
5.  Entomopathogenic fungi, Metarhizium anisopliae and Beauveria bassiana reduce the survival of Xenopsylla brasiliensis larvae (Siphonaptera: Pulicidae) 
Parasites & Vectors  2012;5:204.
Entomopathogenic fungi, particularly those belonging to the genera Metarhizium and Beauveria have shown great promise as arthropod vector control tools. These agents, however, have not been evaluated against flea vectors of plague.
A 3-h exposure to the fungi coated paper at a concentration of 2 × 108 conidia m-2 infected >90% of flea larvae cadavers in the treatment groups. The infection reduced the survival of larvae that had been exposed to fungus relative to controls. The daily risk of dying was four- and over three-fold greater in larvae exposed to M. anisopliae (HR = 4, p<0.001) and B. bassiana (HR = 3.5, p<0.001) respectively. Both fungi can successfully infect and kill larvae of X. brasiliensis with a pooled median survival time (MST±SE) of 2±0.31 days post-exposure.
These findings justify further research to investigate the bio-control potential of entomopathogenic fungi against fleas.
PMCID: PMC3468376  PMID: 22992264
6.  Protective efficacy of menthol propylene glycol carbonate compared to N, N-diethyl-methylbenzamide against mosquito bites in Northern Tanzania 
Parasites & Vectors  2012;5:189.
The reduction of malaria parasite transmission by preventing human-vector contact is critical in lowering disease transmission and its outcomes. This underscores the need for effective and long lasting arthropod/insect repellents. Despite the reduction in malaria transmission and outcomes in Tanzania, personal protection against mosquito bites is still not well investigated. This study sought to determine the efficacy of menthol propylene glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination (blend), both in the laboratory and in the field against Anopheles gambiae s.l and Culex quinquefasciatus.
In the laboratory evaluations, repellents were applied on one arm while the other arm of the same individual was treated with a base cream. Each arm was separately exposed in cages with unfed female mosquitoes. Repellents were evaluated either as a single dose or as a blend. Efficacy of each repellent was determined by the number of mosquitoes that landed and fed on treated arms as compared to the control or among them. In the field, evaluations were performed by human landing catches at hourly intervals from 18:00 hr to 01:00 hr.
A total of 2,442 mosquitoes were collected during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66 (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar protective efficacy ranging from 92% to 100 for both single compound and blends. These findings indicate that MR08 has a similar protective efficacy as DEET for personal protection outside bed nets when used singly and in blends. Because of the personal protection provided by MR08, DEET and blends as topical applicants in laboratory and field situations, these findings suggest that, these repellents could be used efficiently in the community to complement existing tools. Overall, Cx. quinquefasciatus were significantly prevented from blood feeding compared to An. gambiae s.l.
The incorporation of these topical repellents for protection against insect bites can be of additional value in the absence or presence of IRS and ITNs coverage. However, a combination of both the physical (bed nets) and the repellent should be used in an integrated manner for maximum protection, especially before going to bed. Additional research is needed to develop repellents with longer duration of protection.
PMCID: PMC3444865  PMID: 22950604
7.  Social economic factors and malaria transmission in Lower Moshi, Northern Tanzania 
Parasites & Vectors  2012;5:129.
For many years social economic status has been used as an indicator to characterize malaria treatment seeking behaviors of communities and their adherence to malaria control programs. The present study was therefore conducted to assess the influence of household social economic status, knowledge, attitude and practice on treatment seeking behaviors, distance to health facilities and vector control measures in the Lower Moshi area, northern Tanzania.
A cross-sectional household survey was carried out, a quantitative method was used to collect information from the households, and the household socio-economic status was estimated by employing a household asset-based approach. The structured questionnaire also collected information on malaria knowledge, attitudes and treatment seeking behaviors.
A total of 197 (68.8% were female) household heads were interviewed. Distance to the health centers influenced malaria treatment seeking behaviors especially for children (P = 0.001) and the number of visits to the health facilities made by the household members (P = 0.001). The head of the households' level of education had an influence on bed-net retreatment (P < 0.001) and acceptability of larval control programmes (P <0.001). Similarly, a significant association was observed between bed-net retreatment, larval control and occupation of the head of the household .
Distance to the health centre influenced malaria treatment seeking behaviors, and the number of visits made by the household members. In addition, the education level of the household heads played a role in understanding and in the selection of malaria interventions for the households. Increasing the number of health facilities close to rural areas will improve malaria treatment seeking behavior, case management and hence reduce malaria-associated morbidities, especially in high risk groups.
PMCID: PMC3425329  PMID: 22741551
8.  Prevalence and predictors of urinary tract infection and severe malaria among febrile children attending Makongoro health centre in Mwanza city, North-Western Tanzania 
In malaria endemic areas, fever has been used as an entry point for presumptive treatment of malaria. At present, the decrease in malaria transmission in Africa implies an increase in febrile illnesses related to other causes among underfives. Moreover, it is estimated that more than half of the children presenting with fever to public clinics in Africa do not have a malaria infection. Thus, for a better management of all febrile illnesses among under-fives, it becomes relevant to understand the underlying aetiology of the illness. The present study was conducted to determine the relative prevalence and predictors of P. falciparum malaria, urinary tract infections and bacteremia among under-fives presenting with a febrile illness at the Makongoro Primary Health Centre, North-Western Tanzania.
From February to June 2011, a cross-sectional analytical survey was conducted among febrile children less than five years of age. Demographic and clinical data were collected using a standardized pre-tested questionnaire. Blood and urine culture was done, followed by the identification of isolates using in-house biochemical methods. Susceptibility patterns to commonly used antibiotics were investigated using the disc diffusion method. Giemsa stained thin and thick blood smears were examined for any malaria parasites stages.
A total of 231 febrile under-fives were enrolled in the study. Of all the children, 20.3% (47/231, 95%CI, 15.10-25.48), 9.5% (22/231, 95%CI, 5.72-13.28) and 7.4% (17/231, 95%CI, 4.00-10.8) had urinary tract infections, P. falciparum malaria and bacteremia respectively. In general, 11.5% (10/87, 95%CI, 8.10-14.90) of the children had two infections and only one child had all three infections. Predictors of urinary tract infections (UTI) were dysuria (OR = 12.51, 95% CI, 4.28-36.57, P < 0.001) and body temperature (40-41 C) (OR = 12.54, 95% CI, 4.28-36.73, P < 0.001). Predictors of P. falciparum severe malaria were pallor (OR = 4.66 95%CI, 1.21-17.8, P = 0.025) and convulsion (OR = 102, 95% CI, 10-996, P = 0.001). Escherichia coli were the common gram negative isolates from urine (72.3%, 95% CI, 66.50-78.10) and blood (40%, 95%CI, and 33.70-46.30). Escherichia coli from urine were 100% resistant to ampicillin, 97% resistant to co-trimoxazole, 85% resistant to augmentin and 32.4% resistant to gentamicin; and they were 100%, 91.2% and 73.5% sensitive to meropenem, ciprofloxacin and ceftriaxone respectively.
Urinary tract infection caused by multi drug resistant Escherichia coli was the common cause of febrile illness in our setting. Improvement of malaria diagnosis and its differential diagnosis from other causes of febrile illnesses may provide effective management of febrile illnesses among children in Tanzania
PMCID: PMC3415110  PMID: 22958592
Fever; Malaria; Urinary tract infection; Bacteremia; Under-fives; Tanzania
9.  Confirmed malaria cases among children under five with fever and history of fever in rural western Tanzania 
BMC Research Notes  2011;4:359.
The World Health Organization recommends that malaria treatment should begin with parasitological diagnosis. This will help to control misuse of anti-malarial drugs in areas with low transmission. The present study was conducted to assess the prevalence of parasitologically confirmed malaria among children under five years of age presenting with fever or history of fever in rural western Tanzania. A finger prick blood sample was obtained from each child, and thin and thick blood smears were prepared, stained with 10% Giemsa and examined under the light microscope. A structured questionnaire was used to collect each patient's demographic information, reasons for coming to the health center; and a physical examination was carried out on all patients. Fever was defined as axillary temperature ≥ 37.5°C.
A total of 300 children with fever or a history of fever (1 or 2 weeks) were recruited, in which 54.3% (163/300, 95%CI, 48.7-59.9) were boys. A total of 76 (76/300, 25.3%, 95%CI, 22.8 - 27.8) of the children had fever. Based on a parasitological diagnosis of malaria, only 12% (36/300, 95%CI, 8.3-15.7) of the children had P. falciparum infection. Of the children with P. falciparum infection, 52.7% (19/36, 95%CI, 47.1-58.3) had fever and the remaining had no fever. The geometrical mean of the parasites was 708.62 (95%CI, 477.96-1050.62) parasites/μl and 25% (9/36, 95%CI, 10.9 -- 39.1) of the children with positive P. falciparum had ≥ 1001 parasites/μl. On Univariate (OR = 2.13, 95%CI, 1.02-4.43, P = 0.044) and multivariate (OR = 2.15, 95%CI, 1.03-4.49) analysis, only children above one year of age were associated with malaria infections.
Only a small proportion of the children under the age of five with fever had malaria, and with a proportion of children having non-malaria fever. Improvement of malaria diagnostic and other causes of febrile illness may provide effective measure in management of febrile illness in malaria endemic areas.
PMCID: PMC3180709  PMID: 21914203
Fever; history of fever; parasitological diagnosis; western Tanzania
10.  Durability associated efficacy of long-lasting insecticidal nets after five years of household use 
Parasites & Vectors  2011;4:156.
Long-lasting insecticidal nets (LLINs) have been strongly advocated for use to prevent malaria in sub-Saharan Africa and have significantly reduced human-vector contact. PermaNet® 2.0 is among the five LLINs brands which have been given full approval by the WHO Pesticide Evaluation Scheme (WHOPES). The LLINs are expected to protect the malaria endemic communities, but a number of factors within the community can affect their durability and efficacy. This study evaluated the durability, efficacy and retention of PermaNet® 2.0 after five years of use in a Tanzanian community.
Two to three day- old non blood-fed female mosquitoes from an insectary susceptible colony (An. gambiae s.s, this colony was established at TPRI from Kisumu, Kenya in 1992) and wild mosquito populations (An. arabiensis and Culex quinquefasciatus) were used in cone bioassay tests to assess the efficacy of mosquito nets.
The knockdown effect was recorded after three minutes of exposure, and mortality was recorded after 24 hours post-exposure. Mortality of An. gambiae s.s from insectary colony was 100% while An. arabiensis and Cx.quinquefasciatus wild populations had reduced mortality. Insecticide content of the new (the bed net of the same brand but never used before) and used PermaNet® 2.0 was determined using High Performance Liquid Chromatography (HPLC).
The results of this study suggest that, in order to achieve maximum protection against malaria, public health education focusing on bed net use and maintenance should be incorporated into the mass distribution of nets in communities.
PMCID: PMC3174122  PMID: 21819578
11.  HIV, appendectomy and postoperative complications at a reference hospital in Northwest Tanzania: cross-sectional study 
Appendicitis is a frequent surgical emergency worldwide. The present study was conducted to determine the prevalence of HIV, and the association of infection with clinical, intraoperative and histological findings and outcome, among patients with appendicitis.
We performed a cross sectional study at Weill-Bugando Medical Centre in northwest Tanzania. In total, 199 patients undergoing appendectomy were included. Demographic characteristics of patients, clinical features, laboratory, intraoperative and histopathological findings, and HIV serostatus were recorded.
In total, 26/199 (13.1%) were HIV-seropositive. The HIV-positive population was significantly older (mean age: 38.4 years) than the HIV-negative population (25.3 years; p < 0.001). Leukocytosis was present in 87% of seronegative patients, as compared to 34% in seropositive patients (p = 0.0001), and peritonitis was significantly more frequent among HIV-positives (31% vs. 2%; p < 0.001). The mean (SD) length of hospital stay was significantly longer in HIV-positives (7.12 ± 2.94 days vs. 4.02 ± 1.14 days; p < 0.001); 11.5% of HIV patients developed surgical site infections, as compared to 0.6% in the HIV-negative group (p = 0.004).
HIV infections are common among patients with appendicitis in Tanzania, and are associated with severe morbidity, postoperative complications and longer hospital stays. Early diagnosis of appendicitis and prompt appendectomy are crucial in areas with high prevalence of HIV infection. Routine pre-test counseling and HIV screening for appendicitis patients is recommended to detect early cases who may benefit from HAART.
PMCID: PMC3022665  PMID: 21190572
12.  Retrospective Analysis of Suspected Rabies Cases Reported at Bugando Referral Hospital, Mwanza, Tanzania 
The aim of this study was to determine the incidence of humans being bitten by rabies-suspected animals, and the victims’ adherence to post-exposure prophylaxis (PEP) regimen.
Materials and Methods:
A retrospective analysis of data of victims treated at Bugando Medical Centre during the period 2002-2006 (n=5 years) was done.
A total of 767 bite injuries inflicted by rabies-suspected animals were reported, giving a mean annual incidence of ~58 cases per 100,000 (52.5% males, 47.5% females). The proportion of children bitten was relatively higher than that of adults. All victims were treated by using inactivated diploid-cell rabies vaccine and were recommended to appear for the second and third doses. However, only 28% of the victims completed the vaccination regime. Domestic dogs were involved in 95.44% of the human bite cases, whereas cats (3.9%), spotted hyena (Crocuta crocuta) (0.03%), vervet monkey (Cercopithecur aethiops) (0.01%) and black-backed jackal (0.01%) played a minor role. The majority of rabies-suspected case reports were from Nyamagana district and occurred most frequently from June to October each year.
In conclusion, this study revealed that incidences of humans being bitten by dogs suspected of rabies are common in Tanzania, involve mostly children, and victims do not comply with the prophylactic regimen. Rigorous surveillance to determine the status of rabies and the risk factors for human rabies, as well as formulation and institution of appropriate rabies-control policies, is required.
PMCID: PMC2946675  PMID: 20927280
Bugando hospital; Human animal bites; Mwanza; Rabies; Tanzania
13.  Case Series of Adenocarcinoma of the Prostate Associated with Schistosoma haematobium Infection in Tanzania 
In endemic areas, schistosomiasis has been associated with the pathogenesis of bladder, prostate, colorectal and renal carcinoma. However, the relationship between prostate cancer and schistosomiasis infection remains controversial. Here we present a series of three cases from Tanzania of prostatic adenocarcinoma associated with urinary schistosomiasis.
PMCID: PMC2946689  PMID: 20927294
Adenocarcinoma; Prostate; Schistosoma haematobium; Schistosomiasis; Tanzania
14.  Is aging raw cattle urine efficient for sampling Anopheles arabiensis Patton? 
BMC Infectious Diseases  2010;10:172.
To ensure sustainable routine surveillance of mosquito vectors, simple, effective and ethically acceptable tools are required. As a part of that, we evaluated the efficiency of resting boxes baited with fresh and aging cattle urine for indoor and outdoor sampling of An. arabiensis in the lower Moshi rice irrigation schemes.
A cattle urine treatment and re-treatment schedule was used, including a box with a piece of cloth re-treated with urine daily, and once after 3 and 7 day. Resting box with piece of black cloth not treated with urine was used as a control. Each treatment was made in pair for indoor and outdoor sampling. A 4 by 4 Latin square design was used to achieve equal rotation of each of the four treatments across the experimental houses. Sampling was done over a period of 6 months, once per week.
A total of 7871 mosquitoes were collected throughout the study period. 49.8% of the mosquitoes were collected from resting box treated with urine daily; 21.6% and 20.0% were from boxes treated 3 and 7 days respectively. Only 8.6% were from untreated resting box (control). The proportion collected indoors was ~2 folds greater than the outdoor. Of all mosquitoes, 12.3% were unfed, 4.1% full fed, 34.2% semi-gravid and 49.4% gravid.
Fresh and decaying cattle urine odour baited resting boxes offer an alternative tool for sampling particularly semi-gravid and gravid An. arabiensis. Evaluation in low density seasons of An. arabiensis in different ecological settings remains necessary. This sampling method may be standardized for replacing human landing catch.
PMCID: PMC2896370  PMID: 20550680
15.  Knowledge, Attitudes, and Practices about Malaria and Its Control in Rural Northwest Tanzania 
Malaria Research and Treatment  2010;2010:794261.
Background. We assessed community knowledge, attitudes, and practices on malaria as well as acceptability to indoor residual spraying. Material and Methods. A cross-sectional survey was done in a community in Geita district (northwest Tanzania). Household heads (n = 366) were interviewed Results. Knowledge on malaria transmission, prevention, and treatment was reasonable; 56% of respondents associated the disease with mosquito bites, with a significant difference between education level and knowledge on transmission (P < .001). Knowledge of mosquito breeding areas was also associated with education (illiterate: 22%; literate: 59% (P < .001). Bed nets were used by 236 (64.5%), and usage was significantly associated with education level (P < .01). The level of bed net ownership was 77.3%. Most respondents (86.3%) agreed with indoor residual spraying of insecticides. Health facilities were the first option for malaria treatment by 47.3%. Artemether-lumefantrine was the most common antimalarial therapy used. Conclusions. Despite reasonable knowledge on malaria and its preventive measures, there is a need to improve availability of information through proper community channels. Special attention should be given to illiterate community members. High acceptance of indoor residual spraying and high level of bed net ownership should be taken as an advantage to improve malaria control.
PMCID: PMC3275933  PMID: 22332023
16.  Co-infections with Plasmodium falciparum, Schistosoma mansoni and intestinal helminths among schoolchildren in endemic areas of northwestern Tanzania 
Parasites & Vectors  2010;3:44.
Malaria, schistosomiasis and intestinal helminth infections are causes of high morbidity in most tropical parts of the world. Even though these infections often co-exist, most studies focus on individual diseases. In the present study, we investigated the prevalence of Plasmodium falciparum-malaria, intestinal schistosomiasis, soil-transmitted helminth infections, and the respective co-infections, among schoolchildren in northwest Tanzania.
A cross sectional study was conducted among schoolchildren living in villages located close to the shores of Lake Victoria. The Kato Katz technique was employed to screen faecal samples for S. mansoni and soil-transmitted helminth eggs. Giemsa stained thick and thin blood smears were analysed for the presence of malaria parasites.
Of the 400 children included in the study, 218 (54.5%) were infected with a single parasite species, 116 (29%) with two or more species, and 66 (16.5%) had no infection. The prevalences of P. falciparum and S. mansoni were 13.5% (95% CI, 10.2-16.8), and 64.3% (95% CI, 59.6-68.9) respectively. Prevalence of hookworm infection was 38% (95% CI, 33.2-42.8). A. lumbricoides and T. trichiura were not detected. Of the children 26.5% (95% CI, 21.9-30.6) that harbored two parasite species, combination of S. mansoni and hookworm co-infections was the most common (69%). Prevalence of S. mansoni - P. falciparum co-infections was 22.6% (95%CI, 15.3-31.3) and that of hookworm - P. falciparum co-infections 5.7% (95%CI, 2.6-12.8). Prevalence of co-infection of P. falciparum, S. mansoni and hookworm was 2.8% (95%CI, 1.15-4.4).
Multiple parasitic infections are common among schoolchildren in rural northwest Tanzania. These findings can be used for the design and implementation of sound intervention strategies to mitigate morbidity and co-morbidity.
PMCID: PMC2881914  PMID: 20482866

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